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Published in: NeuroMolecular Medicine 2/2010

01-06-2010 | Original Paper

The Role of the Complement System and the Activation Fragment C5a in the Central Nervous System

Authors: Trent M. Woodruff, Rahasson R. Ager, Andrea J. Tenner, Peter G. Noakes, Stephen M. Taylor

Published in: NeuroMolecular Medicine | Issue 2/2010

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Abstract

The complement system is a pivotal component of the innate immune system which protects the host from infection and injury. Complement proteins can be induced in all cell types within the central nervous system (CNS), where the pathway seems to play similar roles in host defense. Complement activation produces the C5 cleavage fragment C5a, a potent inflammatory mediator, which recruits and activates immune cells. The primary cellular receptor for C5a, the C5a receptor (CD88), has been reported to be on all CNS cells, including neurons and glia, suggesting a functional role for C5a in the CNS. A second receptor for C5a, the C5a-like receptor 2 (C5L2), is also expressed on these cells; however, little is currently known about its potential role in the CNS. The potent immune and inflammatory actions of complement activation are necessary for host defense. However, if over-activated, or left unchecked it promotes tissue injury and contributes to brain disease pathology. Thus, complement activation, and subsequent C5a generation, is thought to play a significant role in the progression of CNS disease. Paradoxically, complement may also exert a neuroprotective role in these diseases by aiding in the elimination of aggregated and toxic proteins and debris which are a principal hallmark of many of these diseases. This review will discuss the expression and known roles for complement in the CNS, with a particular focus on the pro-inflammatory end-product, C5a. The possible overarching role for C5a in diseases of the CNS is reviewed, and the therapeutic potential of blocking C5a/CD88 interaction is evaluated.
Literature
go back to reference Afagh, A., Cummings, B. J., Cribbs, D. H., Cotman, C. W., & Tenner, A. J. (1996). Localization and cell association of C1q in Alzheimer’s disease brain. Experimental Neurology, 138, 22–32.PubMed Afagh, A., Cummings, B. J., Cribbs, D. H., Cotman, C. W., & Tenner, A. J. (1996). Localization and cell association of C1q in Alzheimer’s disease brain. Experimental Neurology, 138, 22–32.PubMed
go back to reference Akiyama, H., Arai, T., Kondo, H., Tanno, E., Haga, C., & Ikeda, K. (2000). Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Disease and Associated Disorders, 14(Suppl 1), S47–S53.PubMed Akiyama, H., Arai, T., Kondo, H., Tanno, E., Haga, C., & Ikeda, K. (2000). Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Disease and Associated Disorders, 14(Suppl 1), S47–S53.PubMed
go back to reference Ames, R. S., Li, Y., Sarau, H. M., Nuthulaganti, P., Foley, J. J., Ellis, C., et al. (1996). Molecular cloning and characterization of the human anaphylatoxin C3a receptor. Journal of Biological Chemistry, 271, 20231–20234.PubMed Ames, R. S., Li, Y., Sarau, H. M., Nuthulaganti, P., Foley, J. J., Ellis, C., et al. (1996). Molecular cloning and characterization of the human anaphylatoxin C3a receptor. Journal of Biological Chemistry, 271, 20231–20234.PubMed
go back to reference Armstrong, R. C., Harvath, L., & Dubois-Dalcq, M. E. (1990). Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules. Journal of Neuroscience Research, 27, 400–407.PubMed Armstrong, R. C., Harvath, L., & Dubois-Dalcq, M. E. (1990). Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules. Journal of Neuroscience Research, 27, 400–407.PubMed
go back to reference Avery, V. M., Adrian, D. L., & Gordon, D. L. (1993). Detection of mosaic protein mRNA in human astrocytes. Immunology and Cell Biology, 71(Pt 3), 215–219.PubMed Avery, V. M., Adrian, D. L., & Gordon, D. L. (1993). Detection of mosaic protein mRNA in human astrocytes. Immunology and Cell Biology, 71(Pt 3), 215–219.PubMed
go back to reference Barnum, S. R., Ishii, Y., Agrawal, A., & Volanakis, J. E. (1992a). Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG. Biochemical Journal, 287(Pt 2), 595–601.PubMed Barnum, S. R., Ishii, Y., Agrawal, A., & Volanakis, J. E. (1992a). Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG. Biochemical Journal, 287(Pt 2), 595–601.PubMed
go back to reference Barnum, S. R., Jones, J. L., & Benveniste, E. N. (1992b). Interferon-gamma regulation of C3 gene expression in human astroglioma cells. Journal of Neuroimmunology, 38, 275–282.PubMed Barnum, S. R., Jones, J. L., & Benveniste, E. N. (1992b). Interferon-gamma regulation of C3 gene expression in human astroglioma cells. Journal of Neuroimmunology, 38, 275–282.PubMed
go back to reference Barnum, S. R., Jones, J. L., & Benveniste, E. N. (1993). Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells. Glia, 7, 225–236.PubMed Barnum, S. R., Jones, J. L., & Benveniste, E. N. (1993). Interleukin-1 and tumor necrosis factor-mediated regulation of C3 gene expression in human astroglioma cells. Glia, 7, 225–236.PubMed
go back to reference Benard, M., Gonzalez, B. J., Schouft, M. T., Falluel-Morel, A., Vaudry, D., Chan, P., et al. (2004). Characterization of C3a and C5a receptors in rat cerebellar granule neurons during maturation. Neuroprotective effect of C5a against apoptotic cell death. Journal of Biological Chemistry, 279, 43487–43496.PubMed Benard, M., Gonzalez, B. J., Schouft, M. T., Falluel-Morel, A., Vaudry, D., Chan, P., et al. (2004). Characterization of C3a and C5a receptors in rat cerebellar granule neurons during maturation. Neuroprotective effect of C5a against apoptotic cell death. Journal of Biological Chemistry, 279, 43487–43496.PubMed
go back to reference Benard, M., Raoult, E., Vaudry, D., Leprince, J., Falluel-Morel, A., Gonzalez, B. J., et al. (2008). Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Molecular Immunology, 45, 3767–3774.PubMed Benard, M., Raoult, E., Vaudry, D., Leprince, J., Falluel-Morel, A., Gonzalez, B. J., et al. (2008). Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum. Molecular Immunology, 45, 3767–3774.PubMed
go back to reference Biro, A., Rovo, Z., Papp, D., Cervenak, L., Varga, L., Fust, G., et al. (2007). Studies on the interactions between C-reactive protein and complement proteins. Immunology, 121, 40–50.PubMed Biro, A., Rovo, Z., Papp, D., Cervenak, L., Varga, L., Fust, G., et al. (2007). Studies on the interactions between C-reactive protein and complement proteins. Immunology, 121, 40–50.PubMed
go back to reference Bohlson, S. S., Fraser, D. A., & Tenner, A. J. (2007). Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions. Molecular Immunology, 44, 33–43.PubMed Bohlson, S. S., Fraser, D. A., & Tenner, A. J. (2007). Complement proteins C1q and MBL are pattern recognition molecules that signal immediate and long-term protective immune functions. Molecular Immunology, 44, 33–43.PubMed
go back to reference Boos, L., Campbell, I. L., Ames, R., Wetsel, R. A., & Barnum, S. R. (2004). Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis. Journal of Immunology, 173, 4708–4714. Boos, L., Campbell, I. L., Ames, R., Wetsel, R. A., & Barnum, S. R. (2004). Deletion of the complement anaphylatoxin C3a receptor attenuates, whereas ectopic expression of C3a in the brain exacerbates, experimental autoimmune encephalomyelitis. Journal of Immunology, 173, 4708–4714.
go back to reference Bradt, B. M., Kolb, W. P., & Cooper, N. R. (1998). Complement-dependent proinflammatory properties of the Alzheimer’s disease beta-peptide. Journal of Experimental Medicine, 188, 431–438.PubMed Bradt, B. M., Kolb, W. P., & Cooper, N. R. (1998). Complement-dependent proinflammatory properties of the Alzheimer’s disease beta-peptide. Journal of Experimental Medicine, 188, 431–438.PubMed
go back to reference Cain, S. A., & Monk, P. N. (2002). The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). Journal of Biological Chemistry, 277, 7165–7169.PubMed Cain, S. A., & Monk, P. N. (2002). The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). Journal of Biological Chemistry, 277, 7165–7169.PubMed
go back to reference Chen, N., & Reiss, C. S. (2002). Innate immunity in viral encephalitis: Role of C5. Viral Immunology, 15, 365–372.PubMed Chen, N., & Reiss, C. S. (2002). Innate immunity in viral encephalitis: Role of C5. Viral Immunology, 15, 365–372.PubMed
go back to reference Cole, D. S., Hughes, T. R., Gasque, P., & Morgan, B. P. (2006). Complement regulator loss on apoptotic neuronal cells causes increased complement activation and promotes both phagocytosis and cell lysis. Molecular Immunology, 43, 1953–1964.PubMed Cole, D. S., Hughes, T. R., Gasque, P., & Morgan, B. P. (2006). Complement regulator loss on apoptotic neuronal cells causes increased complement activation and promotes both phagocytosis and cell lysis. Molecular Immunology, 43, 1953–1964.PubMed
go back to reference Cowell, R. M., Plane, J. M., & Silverstein, F. S. (2003). Complement activation contributes to hypoxic–ischemic brain injury in neonatal rats. Journal of Neuroscience, 23, 9459–9468.PubMed Cowell, R. M., Plane, J. M., & Silverstein, F. S. (2003). Complement activation contributes to hypoxic–ischemic brain injury in neonatal rats. Journal of Neuroscience, 23, 9459–9468.PubMed
go back to reference Cudrici, C., Niculescu, T., Niculescu, F., Shin, M. L., & Rus, H. (2006). Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement. Journal of Rehabilitation Research and Development, 43, 123–132.PubMed Cudrici, C., Niculescu, T., Niculescu, F., Shin, M. L., & Rus, H. (2006). Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement. Journal of Rehabilitation Research and Development, 43, 123–132.PubMed
go back to reference Daveau, M., Benard, M., Scotte, M., Schouft, M. T., Hiron, M., Francois, A., et al. (2004). Expression of a functional C5a receptor in regenerating hepatocytes and its involvement in a proliferative signaling pathway in rat. Journal of Immunology, 173, 3418–3424. Daveau, M., Benard, M., Scotte, M., Schouft, M. T., Hiron, M., Francois, A., et al. (2004). Expression of a functional C5a receptor in regenerating hepatocytes and its involvement in a proliferative signaling pathway in rat. Journal of Immunology, 173, 3418–3424.
go back to reference Davoust, N., Jones, J., Stahel, P. F., Ames, R. S., & Barnum, S. R. (1999). Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells. Glia, 26, 201–211.PubMed Davoust, N., Jones, J., Stahel, P. F., Ames, R. S., & Barnum, S. R. (1999). Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells. Glia, 26, 201–211.PubMed
go back to reference Eikelenboom, P., Hack, C. E., Rozemuller, J. M., & Stam, F. C. (1989). Complement activation in amyloid plaques in Alzheimer’s dementia. Virchows Archiv B, Cell Pathology Including Molecular Pathology, 56, 259–262.PubMed Eikelenboom, P., Hack, C. E., Rozemuller, J. M., & Stam, F. C. (1989). Complement activation in amyloid plaques in Alzheimer’s dementia. Virchows Archiv B, Cell Pathology Including Molecular Pathology, 56, 259–262.PubMed
go back to reference Farkas, I., Baranyi, L., Kaneko, Y., Liposits, Z., Yamamoto, T., & Okada, H. (1999). C5a receptor expression by TGW neuroblastoma cells. Neuroreport, 10, 3021–3025.PubMed Farkas, I., Baranyi, L., Kaneko, Y., Liposits, Z., Yamamoto, T., & Okada, H. (1999). C5a receptor expression by TGW neuroblastoma cells. Neuroreport, 10, 3021–3025.PubMed
go back to reference Farkas, I., Baranyi, L., Liposits, Z. S., Yamamoto, T., & Okada, H. (1998). Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells. Neuroscience, 86, 903–911.PubMed Farkas, I., Baranyi, L., Liposits, Z. S., Yamamoto, T., & Okada, H. (1998). Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells. Neuroscience, 86, 903–911.PubMed
go back to reference Farkas, I., Takahashi, M., Fukuda, A., Yamamoto, N., Akatsu, H., Baranyi, L., et al. (2003). Complement C5a receptor-mediated signaling may be involved in neurodegeneration in Alzheimer’s disease. Journal of Immunology, 170, 5764–5771. Farkas, I., Takahashi, M., Fukuda, A., Yamamoto, N., Akatsu, H., Baranyi, L., et al. (2003). Complement C5a receptor-mediated signaling may be involved in neurodegeneration in Alzheimer’s disease. Journal of Immunology, 170, 5764–5771.
go back to reference Ferraiuolo, L., Heath, P. R., Holden, H., Kasher, P., Kirby, J., & Shaw, P. J. (2007). Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. Journal of Neuroscience, 27, 9201–9219.PubMed Ferraiuolo, L., Heath, P. R., Holden, H., Kasher, P., Kirby, J., & Shaw, P. J. (2007). Microarray analysis of the cellular pathways involved in the adaptation to and progression of motor neuron injury in the SOD1 G93A mouse model of familial ALS. Journal of Neuroscience, 27, 9201–9219.PubMed
go back to reference Fonseca, M. I., Ager, R. R., Chu, S. H., Yazan, O., Sanderson, S. D., LaFerla, F. M., et al. (2009). Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer’s disease. Journal of Immunology, 183, 1375–1383. Fonseca, M. I., Ager, R. R., Chu, S. H., Yazan, O., Sanderson, S. D., LaFerla, F. M., et al. (2009). Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer’s disease. Journal of Immunology, 183, 1375–1383.
go back to reference Fonseca, M. I., Kawas, C. H., Troncoso, J. C., & Tenner, A. J. (2004a). Neuronal localization of C1q in preclinical Alzheimer’s disease. Neurobiology of Diseases, 15, 40–46. Fonseca, M. I., Kawas, C. H., Troncoso, J. C., & Tenner, A. J. (2004a). Neuronal localization of C1q in preclinical Alzheimer’s disease. Neurobiology of Diseases, 15, 40–46.
go back to reference Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004b). Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer’s disease. Journal of Neuroscience, 24, 6457–6465.PubMed Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004b). Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer’s disease. Journal of Neuroscience, 24, 6457–6465.PubMed
go back to reference Fukada, Y., Yasui, K., Kitayama, M., Doi, K., Nakano, T., Watanabe, Y., et al. (2007). Gene expression analysis of the murine model of amyotrophic lateral sclerosis: Studies of the Leu126delTT mutation in SOD1. Brain Research, 1160, 1–10.PubMed Fukada, Y., Yasui, K., Kitayama, M., Doi, K., Nakano, T., Watanabe, Y., et al. (2007). Gene expression analysis of the murine model of amyotrophic lateral sclerosis: Studies of the Leu126delTT mutation in SOD1. Brain Research, 1160, 1–10.PubMed
go back to reference Gao, H., Neff, T. A., Guo, R. F., Speyer, C. L., Sarma, J. V., Tomlins, S., et al. (2005). Evidence for a functional role of the second C5a receptor C5L2. FASEB Journal, 19, 1003–1005.PubMed Gao, H., Neff, T. A., Guo, R. F., Speyer, C. L., Sarma, J. V., Tomlins, S., et al. (2005). Evidence for a functional role of the second C5a receptor C5L2. FASEB Journal, 19, 1003–1005.PubMed
go back to reference Garrett, M. C., Otten, M. L., Starke, R. M., Komotar, R. J., Magotti, P., Lambris, J. D., et al.. (2009). Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Research. Garrett, M. C., Otten, M. L., Starke, R. M., Komotar, R. J., Magotti, P., Lambris, J. D., et al.. (2009). Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Research.
go back to reference Gasque, P., Chan, P., Fontaine, M., Ischenko, A., Lamacz, M., Gotze, O., et al. (1995a). Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes. Journal of Immunology, 155, 4882–4889. Gasque, P., Chan, P., Fontaine, M., Ischenko, A., Lamacz, M., Gotze, O., et al. (1995a). Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes. Journal of Immunology, 155, 4882–4889.
go back to reference Gasque, P., Chan, P., Mauger, C., Schouft, M. T., Singhrao, S., Dierich, M. P., et al. (1996b). Identification and characterization of complement C3 receptors on human astrocytes. Journal of Immunology, 156, 2247–2255. Gasque, P., Chan, P., Mauger, C., Schouft, M. T., Singhrao, S., Dierich, M. P., et al. (1996b). Identification and characterization of complement C3 receptors on human astrocytes. Journal of Immunology, 156, 2247–2255.
go back to reference Gasque, P., Dean, Y. D., McGreal, E. P., VanBeek, J., & Morgan, B. P. (2000). Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology, 49, 171–186.PubMed Gasque, P., Dean, Y. D., McGreal, E. P., VanBeek, J., & Morgan, B. P. (2000). Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology, 49, 171–186.PubMed
go back to reference Gasque, P., Fontaine, M., & Morgan, B. P. (1995b). Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. Journal of Immunology, 154, 4726–4733. Gasque, P., Fontaine, M., & Morgan, B. P. (1995b). Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. Journal of Immunology, 154, 4726–4733.
go back to reference Gasque, P., Ischenko, A., Legoedec, J., Mauger, C., Schouft, M. T., & Fontaine, M. (1993). Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells. Journal of Biological Chemistry, 268, 25068–25074.PubMed Gasque, P., Ischenko, A., Legoedec, J., Mauger, C., Schouft, M. T., & Fontaine, M. (1993). Expression of the complement classical pathway by human glioma in culture. A model for complement expression by nerve cells. Journal of Biological Chemistry, 268, 25068–25074.PubMed
go back to reference Gasque, P., Julen, N., Ischenko, A. M., Picot, C., Mauger, C., Chauzy, C., et al. (1992). Expression of complement components of the alternative pathway by glioma cell lines. Journal of Immunology, 149, 1381–1387. Gasque, P., Julen, N., Ischenko, A. M., Picot, C., Mauger, C., Chauzy, C., et al. (1992). Expression of complement components of the alternative pathway by glioma cell lines. Journal of Immunology, 149, 1381–1387.
go back to reference Gasque, P., & Morgan, B. P. (1996). Complement regulatory protein expression by a human oligodendrocyte cell line: Cytokine regulation and comparison with astrocytes. Immunology, 89, 338–347.PubMed Gasque, P., & Morgan, B. P. (1996). Complement regulatory protein expression by a human oligodendrocyte cell line: Cytokine regulation and comparison with astrocytes. Immunology, 89, 338–347.PubMed
go back to reference Gasque, P., Singhrao, S. K., Neal, J. W., Gotze, O., & Morgan, B. P. (1997). Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. American Journal of Pathology, 150, 31–41.PubMed Gasque, P., Singhrao, S. K., Neal, J. W., Gotze, O., & Morgan, B. P. (1997). Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. American Journal of Pathology, 150, 31–41.PubMed
go back to reference Gasque, P., Singhrao, S. K., Neal, J. W., Wang, P., Sayah, S., Fontaine, M., et al. (1998). The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. Journal of Immunology, 160, 3543–3554. Gasque, P., Singhrao, S. K., Neal, J. W., Wang, P., Sayah, S., Fontaine, M., et al. (1998). The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. Journal of Immunology, 160, 3543–3554.
go back to reference Gasque, P., Thomas, A., Fontaine, M., & Morgan, B. P. (1996a). Complement activation on human neuroblastoma cell lines in vitro: Route of activation and expression of functional complement regulatory proteins. Journal of Neuroimmunology, 66, 29–40.PubMed Gasque, P., Thomas, A., Fontaine, M., & Morgan, B. P. (1996a). Complement activation on human neuroblastoma cell lines in vitro: Route of activation and expression of functional complement regulatory proteins. Journal of Neuroimmunology, 66, 29–40.PubMed
go back to reference Gavrilyuk, V., Kalinin, S., Hilbush, B. S., Middlecamp, A., McGuire, S., Pelligrino, D., et al. (2005). Identification of complement 5a-like receptor (C5L2) from astrocytes: Characterization of anti-inflammatory properties. Journal of Neurochemistry, 92, 1140–1149.PubMed Gavrilyuk, V., Kalinin, S., Hilbush, B. S., Middlecamp, A., McGuire, S., Pelligrino, D., et al. (2005). Identification of complement 5a-like receptor (C5L2) from astrocytes: Characterization of anti-inflammatory properties. Journal of Neurochemistry, 92, 1140–1149.PubMed
go back to reference Gerard, N. P., & Gerard, C. (1991). The chemotactic receptor for human C5a anaphylatoxin. Nature, 349, 614–617.PubMed Gerard, N. P., & Gerard, C. (1991). The chemotactic receptor for human C5a anaphylatoxin. Nature, 349, 614–617.PubMed
go back to reference Gerard, N. P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., et al. (2005). An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. Journal of Biological Chemistry, 280, 39677–39680.PubMed Gerard, N. P., Lu, B., Liu, P., Craig, S., Fujiwara, Y., Okinaga, S., et al. (2005). An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. Journal of Biological Chemistry, 280, 39677–39680.PubMed
go back to reference Gordon, D. L., Avery, V. M., Adrian, D. L., & Sadlon, T. A. (1992a). Detection of complement protein mRNA in human astrocytes by the polymerase chain reaction. Journal of Neuroscience Methods, 45, 191–197.PubMed Gordon, D. L., Avery, V. M., Adrian, D. L., & Sadlon, T. A. (1992a). Detection of complement protein mRNA in human astrocytes by the polymerase chain reaction. Journal of Neuroscience Methods, 45, 191–197.PubMed
go back to reference Gordon, D. L., Sadlon, T. A., Wesselingh, S. L., Russell, S. M., Johnstone, R. W., & Purcell, D. F. (1992b). Human astrocytes express membrane cofactor protein (CD46), a regulator of complement activation. Journal of Neuroimmunology, 36, 199–208.PubMed Gordon, D. L., Sadlon, T. A., Wesselingh, S. L., Russell, S. M., Johnstone, R. W., & Purcell, D. F. (1992b). Human astrocytes express membrane cofactor protein (CD46), a regulator of complement activation. Journal of Neuroimmunology, 36, 199–208.PubMed
go back to reference Griffin, R. S., Costigan, M., Brenner, G. J., Ma, C. H. E., Scholz, J., Moss, A., et al. (2007). Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. Journal of Neuroscience, 27, 8699–8708.PubMed Griffin, R. S., Costigan, M., Brenner, G. J., Ma, C. H. E., Scholz, J., Moss, A., et al. (2007). Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. Journal of Neuroscience, 27, 8699–8708.PubMed
go back to reference Haviland, D. L., McCoy, R. L., Whitehead, W. T., Akama, H., Molmenti, E. P., Brown, A., et al. (1995). Cellular expression of the C5a anaphylatoxin receptor (C5aR): Demonstration of C5aR on nonmyeloid cells of the liver and lung. Journal of Immunology, 154, 1861–1869. Haviland, D. L., McCoy, R. L., Whitehead, W. T., Akama, H., Molmenti, E. P., Brown, A., et al. (1995). Cellular expression of the C5a anaphylatoxin receptor (C5aR): Demonstration of C5aR on nonmyeloid cells of the liver and lung. Journal of Immunology, 154, 1861–1869.
go back to reference Hosokawa, M., Klegeris, A., Maguire, J., & McGeer, P. L. (2003). Expression of complement messenger RNAs and proteins by human oligodendroglial cells. Glia, 42, 417–423.PubMed Hosokawa, M., Klegeris, A., Maguire, J., & McGeer, P. L. (2003). Expression of complement messenger RNAs and proteins by human oligodendroglial cells. Glia, 42, 417–423.PubMed
go back to reference Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., et al. (2006). Generation of C5a in the absence of C3: A new complement activation pathway. Nature Medicine, 12, 682–687.PubMed Huber-Lang, M., Sarma, J. V., Zetoune, F. S., Rittirsch, D., Neff, T. A., McGuire, S. R., et al. (2006). Generation of C5a in the absence of C3: A new complement activation pathway. Nature Medicine, 12, 682–687.PubMed
go back to reference Huber-Lang, M., Younkin, E. M., Sarma, J. V., Riedemann, N., McGuire, S. R., Lu, K. T., et al. (2002). Generation of C5a by phagocytic cells. The American Journal of Pathology, 161, 1849–1859.PubMed Huber-Lang, M., Younkin, E. M., Sarma, J. V., Riedemann, N., McGuire, S. R., Lu, K. T., et al. (2002). Generation of C5a by phagocytic cells. The American Journal of Pathology, 161, 1849–1859.PubMed
go back to reference Humayun, S., Gohar, M., Volkening, K., Moisse, K., Leystra-Lantz, C., Mepham, J., et al. (2009). The complement factor C5a receptor is upregulated in NFL−/− mouse motor neurons. Journal of Neuroimmunology, 210, 52–62.PubMed Humayun, S., Gohar, M., Volkening, K., Moisse, K., Leystra-Lantz, C., Mepham, J., et al. (2009). The complement factor C5a receptor is upregulated in NFL−/− mouse motor neurons. Journal of Neuroimmunology, 210, 52–62.PubMed
go back to reference Ischenko, A., Sayah, S., Patte, C., Andreev, S., Gasque, P., Schouft, M. T., et al. (1998). Expression of a functional anaphylatoxin C3a receptor by astrocytes. Journal of Neurochemistry, 71, 2487–2496.PubMedCrossRef Ischenko, A., Sayah, S., Patte, C., Andreev, S., Gasque, P., Schouft, M. T., et al. (1998). Expression of a functional anaphylatoxin C3a receptor by astrocytes. Journal of Neurochemistry, 71, 2487–2496.PubMedCrossRef
go back to reference Itagaki, S., Akiyama, H., Saito, H., & McGeer, P. L. (1994). Ultrastructural localization of complement membrane attack complex (MAC)-like immunoreactivity in brains of patients with Alzheimer’s disease. Brain Research, 645, 78–84.PubMed Itagaki, S., Akiyama, H., Saito, H., & McGeer, P. L. (1994). Ultrastructural localization of complement membrane attack complex (MAC)-like immunoreactivity in brains of patients with Alzheimer’s disease. Brain Research, 645, 78–84.PubMed
go back to reference Jiang, H., Burdick, D., Glabe, C. G., Cotman, C. W., & Tenner, A. J. (1994). Beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. Journal of Immunology, 152, 5050–5059. Jiang, H., Burdick, D., Glabe, C. G., Cotman, C. W., & Tenner, A. J. (1994). Beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. Journal of Immunology, 152, 5050–5059.
go back to reference Kim, G. H., Mocco, J., Hahn, D. K., Kellner, C. P., Komotar, R. J., Ducruet, A. F., et al. (2008). Protective effect of C5a receptor inhibition after murine reperfused stroke. Neurosurgery, 63, 122–125; discussion 125–126.PubMed Kim, G. H., Mocco, J., Hahn, D. K., Kellner, C. P., Komotar, R. J., Ducruet, A. F., et al. (2008). Protective effect of C5a receptor inhibition after murine reperfused stroke. Neurosurgery, 63, 122–125; discussion 125–126.PubMed
go back to reference Kleine, T. O., & Benes, L. (2006). Immune surveillance of the human central nervous system (CNS): Different migration pathways of immune cells through the blood–brain barrier and blood–cerebrospinal fluid barrier in healthy persons. Cytometry A, 69, 147–151.PubMed Kleine, T. O., & Benes, L. (2006). Immune surveillance of the human central nervous system (CNS): Different migration pathways of immune cells through the blood–brain barrier and blood–cerebrospinal fluid barrier in healthy persons. Cytometry A, 69, 147–151.PubMed
go back to reference Lacy, M., Jones, J., Whittemore, S. R., Haviland, D. L., Wetsel, R. A., & Barnum, S. R. (1995). Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. Journal of Neuroimmunology, 61, 71–78.PubMed Lacy, M., Jones, J., Whittemore, S. R., Haviland, D. L., Wetsel, R. A., & Barnum, S. R. (1995). Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. Journal of Neuroimmunology, 61, 71–78.PubMed
go back to reference Lee, D. K., George, S. R., Cheng, R., Nguyen, T., Liu, Y., Brown, M., et al. (2001). Identification of four novel human G protein-coupled receptors expressed in the brain. Molecular Brain Research, 86, 13–22.PubMed Lee, D. K., George, S. R., Cheng, R., Nguyen, T., Liu, Y., Brown, M., et al. (2001). Identification of four novel human G protein-coupled receptors expressed in the brain. Molecular Brain Research, 86, 13–22.PubMed
go back to reference Leinhase, I., Holers, V. M., Thurman, J. M., Harhausen, D., Schmidt, O. I., Pietzcker, M., et al. (2006). Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neuroscience, 7, 55.PubMed Leinhase, I., Holers, V. M., Thurman, J. M., Harhausen, D., Schmidt, O. I., Pietzcker, M., et al. (2006). Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neuroscience, 7, 55.PubMed
go back to reference Levi-Strauss, M., & Mallat, M. (1987). Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation. Journal of Immunology, 139, 2361–2366. Levi-Strauss, M., & Mallat, M. (1987). Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation. Journal of Immunology, 139, 2361–2366.
go back to reference Li, K., Sacks, S. H., & Zhou, W. (2007). The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies. Molecular Immunology, 44, 3866–3874.PubMed Li, K., Sacks, S. H., & Zhou, W. (2007). The relative importance of local and systemic complement production in ischaemia, transplantation and other pathologies. Molecular Immunology, 44, 3866–3874.PubMed
go back to reference Liszewski, M. K., Farries, T. C., Lublin, D. M., Rooney, I. A., & Atkinson, J. P. (1996). Control of the complement system. Advances in Immunology, 61, 201–283.PubMed Liszewski, M. K., Farries, T. C., Lublin, D. M., Rooney, I. A., & Atkinson, J. P. (1996). Control of the complement system. Advances in Immunology, 61, 201–283.PubMed
go back to reference Lobsiger, C. S., Boillee, S., & Cleveland, D. W. (2007). Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons. Proceedings of the National Academy of Sciences of the United States of America, 104, 7319–7326.PubMed Lobsiger, C. S., Boillee, S., & Cleveland, D. W. (2007). Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons. Proceedings of the National Academy of Sciences of the United States of America, 104, 7319–7326.PubMed
go back to reference Loeffler, D. A., Camp, D. M., & Bennett, D. A. (2008). Plaque complement activation and cognitive loss in Alzheimer’s disease. Journal of Neuroinflammation, 5, 9.PubMed Loeffler, D. A., Camp, D. M., & Bennett, D. A. (2008). Plaque complement activation and cognitive loss in Alzheimer’s disease. Journal of Neuroinflammation, 5, 9.PubMed
go back to reference Loos, M., & Clas, F. (1987). Antibody-independent killing of gram-negative bacteria via the classical pathway of complement. Immunology Letters, 14, 203–208.PubMed Loos, M., & Clas, F. (1987). Antibody-independent killing of gram-negative bacteria via the classical pathway of complement. Immunology Letters, 14, 203–208.PubMed
go back to reference Mack, W. J., Ducruet, A. F., Hickman, Z. L., Garrett, M. C., Albert, E. J., Kellner, C. P., et al. (2007). Early plasma complement C3a levels correlate with functional outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery, 61, 255–260; discussion 260–261.PubMed Mack, W. J., Ducruet, A. F., Hickman, Z. L., Garrett, M. C., Albert, E. J., Kellner, C. P., et al. (2007). Early plasma complement C3a levels correlate with functional outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery, 61, 255–260; discussion 260–261.PubMed
go back to reference March, D. R., Proctor, L. M., Stoermer, M. J., Sbaglia, R., Abbenante, G., Reid, R. C., et al. (2004). Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Molecular Pharmacology, 65, 868–879.PubMed March, D. R., Proctor, L. M., Stoermer, M. J., Sbaglia, R., Abbenante, G., Reid, R. C., et al. (2004). Potent cyclic antagonists of the complement C5a receptor on human polymorphonuclear leukocytes. Relationships between structures and activity. Molecular Pharmacology, 65, 868–879.PubMed
go back to reference Marjan, J., Xie, Z., & Devine, D. V. (1994). Liposome-induced activation of the classical complement pathway does not require immunoglobulin. Biochimica et Biophysica Acta, 1192, 35–44.PubMed Marjan, J., Xie, Z., & Devine, D. V. (1994). Liposome-induced activation of the classical complement pathway does not require immunoglobulin. Biochimica et Biophysica Acta, 1192, 35–44.PubMed
go back to reference Mason, J. C., Yarwood, H., Sugars, K., Morgan, B. P., Davies, K. A., & Haskard, D. O. (1999). Induction of decay-accelerating factor by cytokines or the membrane-attack complex protects vascular endothelial cells against complement deposition. Blood, 94, 1673–1682.PubMed Mason, J. C., Yarwood, H., Sugars, K., Morgan, B. P., Davies, K. A., & Haskard, D. O. (1999). Induction of decay-accelerating factor by cytokines or the membrane-attack complex protects vascular endothelial cells against complement deposition. Blood, 94, 1673–1682.PubMed
go back to reference Mastellos, D., Germenis, A. E., & Lambris, J. D. (2005). Complement: An inflammatory pathway fulfilling multiple roles at the interface of innate immunity and development. Current Drug Targets. Inflammation and Allergy, 4, 125–127.PubMed Mastellos, D., Germenis, A. E., & Lambris, J. D. (2005). Complement: An inflammatory pathway fulfilling multiple roles at the interface of innate immunity and development. Current Drug Targets. Inflammation and Allergy, 4, 125–127.PubMed
go back to reference McGeer, P. L., Walker, D. G., Akiyama, H., Kawamata, T., Guan, A. L., Parker, C. J., et al. (1991). Detection of the membrane inhibitor of reactive lysis (CD59) in diseased neurons of Alzheimer brain. Brain Research, 544, 315–319.PubMed McGeer, P. L., Walker, D. G., Akiyama, H., Kawamata, T., Guan, A. L., Parker, C. J., et al. (1991). Detection of the membrane inhibitor of reactive lysis (CD59) in diseased neurons of Alzheimer brain. Brain Research, 544, 315–319.PubMed
go back to reference Mead, R. J., Singhrao, S. K., Neal, J. W., Lassmann, H., & Morgan, B. P. (2002). The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. Journal of Immunology, 168, 458–465. Mead, R. J., Singhrao, S. K., Neal, J. W., Lassmann, H., & Morgan, B. P. (2002). The membrane attack complex of complement causes severe demyelination associated with acute axonal injury. Journal of Immunology, 168, 458–465.
go back to reference Mehlhop, E., & Diamond, M. S. (2006). Protective immune responses against West Nile virus are primed by distinct complement activation pathways. Journal of Experimental Medicine, 203, 1371–1381.PubMed Mehlhop, E., & Diamond, M. S. (2006). Protective immune responses against West Nile virus are primed by distinct complement activation pathways. Journal of Experimental Medicine, 203, 1371–1381.PubMed
go back to reference Miller, A. M., & Stella, N. (2009). Microglial cell migration stimulated by ATP and C5a involve distinct molecular mechanisms: Quantification of migration by a novel near-infrared method. Glia, 57, 875–883.PubMed Miller, A. M., & Stella, N. (2009). Microglial cell migration stimulated by ATP and C5a involve distinct molecular mechanisms: Quantification of migration by a novel near-infrared method. Glia, 57, 875–883.PubMed
go back to reference Mocco, J., Wilson, D. A., Komotar, R. J., Sughrue, M. E., Coates, K., Sacco, R. L., et al. (2006). Alterations in plasma complement levels after human ischemic stroke. Neurosurgery, 59, 28–33; discussion 28–33.PubMed Mocco, J., Wilson, D. A., Komotar, R. J., Sughrue, M. E., Coates, K., Sacco, R. L., et al. (2006). Alterations in plasma complement levels after human ischemic stroke. Neurosurgery, 59, 28–33; discussion 28–33.PubMed
go back to reference Moller, T., Nolte, C., Burger, R., Verkhratsky, A., & Kettenmann, H. (1997). Mechanisms of C5a and C3a complement fragment-induced [Ca2+]i signaling in mouse microglia. Journal of Neuroscience, 17, 615–624.PubMed Moller, T., Nolte, C., Burger, R., Verkhratsky, A., & Kettenmann, H. (1997). Mechanisms of C5a and C3a complement fragment-induced [Ca2+]i signaling in mouse microglia. Journal of Neuroscience, 17, 615–624.PubMed
go back to reference Morgan, B. P., Griffiths, M., Khanom, H., Taylor, S. M., & Neal, J. W. (2004). Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats. Clinical and Experimental Immunology, 138, 430–438.PubMed Morgan, B. P., Griffiths, M., Khanom, H., Taylor, S. M., & Neal, J. W. (2004). Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats. Clinical and Experimental Immunology, 138, 430–438.PubMed
go back to reference Mukherjee, P., & Pasinetti, G. M. (2000). The role of complement anaphylatoxin C5a in neurodegeneration: Implications in Alzheimer’s disease. Journal of Neuroimmunology, 105, 124–130.PubMed Mukherjee, P., & Pasinetti, G. M. (2000). The role of complement anaphylatoxin C5a in neurodegeneration: Implications in Alzheimer’s disease. Journal of Neuroimmunology, 105, 124–130.PubMed
go back to reference Mukherjee, P., & Pasinetti, G. M. (2001). Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3. Journal of Neurochemistry, 77, 43–49.PubMed Mukherjee, P., & Pasinetti, G. M. (2001). Complement anaphylatoxin C5a neuroprotects through mitogen-activated protein kinase-dependent inhibition of caspase 3. Journal of Neurochemistry, 77, 43–49.PubMed
go back to reference Mukherjee, P., Thomas, S., & Pasinetti, G. M. (2008). Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo. J Neuroinflammation, 5, 5.PubMed Mukherjee, P., Thomas, S., & Pasinetti, G. M. (2008). Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo. J Neuroinflammation, 5, 5.PubMed
go back to reference Muller-Ladner, U., Jones, J. L., Wetsel, R. A., Gay, S., Raine, C. S., & Barnum, S. R. (1996). Enhanced expression of chemotactic receptors in multiple sclerosis lesions. Journal of the Neurological Sciences, 144, 135–141.PubMed Muller-Ladner, U., Jones, J. L., Wetsel, R. A., Gay, S., Raine, C. S., & Barnum, S. R. (1996). Enhanced expression of chemotactic receptors in multiple sclerosis lesions. Journal of the Neurological Sciences, 144, 135–141.PubMed
go back to reference Nataf, S., Davoust, N., & Barnum, S. R. (1998). Kinetics of anaphylatoxin C5a receptor expression during experimental allergic encephalomyelitis. Journal of Neuroimmunology, 91, 147–155.PubMed Nataf, S., Davoust, N., & Barnum, S. R. (1998). Kinetics of anaphylatoxin C5a receptor expression during experimental allergic encephalomyelitis. Journal of Neuroimmunology, 91, 147–155.PubMed
go back to reference Nataf, S., Levison, S. W., & Barnum, S. R. (2001). Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage. Brain Research, 894, 321–326.PubMed Nataf, S., Levison, S. W., & Barnum, S. R. (2001). Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage. Brain Research, 894, 321–326.PubMed
go back to reference Nolte, C., Moller, T., Walter, T., & Kettenmann, H. (1996). Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton. Neuroscience, 73, 1091–1107.PubMed Nolte, C., Moller, T., Walter, T., & Kettenmann, H. (1996). Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton. Neuroscience, 73, 1091–1107.PubMed
go back to reference Nyakoe, N. K., Taylor, R. P., Makumi, J. N., & Waitumbi, J. N. (2009). Complement consumption in children with Plasmodium falciparum malaria. Malaria Journal, 8, 7.PubMed Nyakoe, N. K., Taylor, R. P., Makumi, J. N., & Waitumbi, J. N. (2009). Complement consumption in children with Plasmodium falciparum malaria. Malaria Journal, 8, 7.PubMed
go back to reference O’Barr, S. A., Caguioa, J., Gruol, D., Perkins, G., Ember, J. A., Hugli, T., et al. (2001). Neuronal expression of a functional receptor for the C5a complement activation fragment. Journal of Immunology, 166, 4154–4162. O’Barr, S. A., Caguioa, J., Gruol, D., Perkins, G., Ember, J. A., Hugli, T., et al. (2001). Neuronal expression of a functional receptor for the C5a complement activation fragment. Journal of Immunology, 166, 4154–4162.
go back to reference O’Barr, S., Yu, J. X., & Cooper, N. R. (1998). Neuronal expression of the C5a receptor. Molecular Immunology, 35, 26. O’Barr, S., Yu, J. X., & Cooper, N. R. (1998). Neuronal expression of the C5a receptor. Molecular Immunology, 35, 26.
go back to reference Ohno, M., Hirata, T., Enomoto, M., Araki, T., Ishimaru, H., & Takahashi, T. A. (2000). A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. Molecular Immunology, 37, 407–412.PubMed Ohno, M., Hirata, T., Enomoto, M., Araki, T., Ishimaru, H., & Takahashi, T. A. (2000). A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. Molecular Immunology, 37, 407–412.PubMed
go back to reference Osaka, H., McGinty, A., Hoepken, U. E., Lu, B., Gerard, C., & Pasinetti, G. M. (1999a). Expression of C5a receptor in mouse brain: Role in signal transduction and neurodegeneration. Neuroscience, 88, 1073–1082.PubMed Osaka, H., McGinty, A., Hoepken, U. E., Lu, B., Gerard, C., & Pasinetti, G. M. (1999a). Expression of C5a receptor in mouse brain: Role in signal transduction and neurodegeneration. Neuroscience, 88, 1073–1082.PubMed
go back to reference Osaka, H., Mukherjee, P., Aisen, P. S., & Pasinetti, G. M. (1999b). Complement-derived anaphylatoxin C5a protects against glutamate-mediated neurotoxicity. Journal of Cellular Biochemistry, 73, 303–311.PubMed Osaka, H., Mukherjee, P., Aisen, P. S., & Pasinetti, G. M. (1999b). Complement-derived anaphylatoxin C5a protects against glutamate-mediated neurotoxicity. Journal of Cellular Biochemistry, 73, 303–311.PubMed
go back to reference Otto, M., Hawlisch, H., Monk, P. N., Muller, M., Klos, A., Karp, C. L., et al. (2004). C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: Position 69 is the locus that determines agonism or antagonism. Journal of Biological Chemistry, 279, 142–151.PubMed Otto, M., Hawlisch, H., Monk, P. N., Muller, M., Klos, A., Karp, C. L., et al. (2004). C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: Position 69 is the locus that determines agonism or antagonism. Journal of Biological Chemistry, 279, 142–151.PubMed
go back to reference Patel, S. N., Berghout, J., Lovegrove, F. E., Ayi, K., Conroy, A., Serghides, L., et al. (2008). C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. Journal of Experimental Medicine, 205, 1133–1143.PubMed Patel, S. N., Berghout, J., Lovegrove, F. E., Ayi, K., Conroy, A., Serghides, L., et al. (2008). C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. Journal of Experimental Medicine, 205, 1133–1143.PubMed
go back to reference Peitsch, M. C., Tschopp, J., Kress, A., & Isliker, H. (1988). Antibody-independent activation of the complement system by mitochondria is mediated by cardiolipin. Biochemical Journal, 249, 495–500.PubMed Peitsch, M. C., Tschopp, J., Kress, A., & Isliker, H. (1988). Antibody-independent activation of the complement system by mitochondria is mediated by cardiolipin. Biochemical Journal, 249, 495–500.PubMed
go back to reference Persson, M., Pekna, M., Hansson, E., & Ronnback, L. (2009). The complement-derived anaphylatoxin C5a increases microglial GLT-1 expression and glutamate uptake in a TNF-alpha-independent manner. European Journal of Neuroscience, 29, 267–274.PubMed Persson, M., Pekna, M., Hansson, E., & Ronnback, L. (2009). The complement-derived anaphylatoxin C5a increases microglial GLT-1 expression and glutamate uptake in a TNF-alpha-independent manner. European Journal of Neuroscience, 29, 267–274.PubMed
go back to reference Pisalyaput, K., & Tenner, A. J. (2008). Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms. Journal of Neurochemistry, 104, 696–707.PubMed Pisalyaput, K., & Tenner, A. J. (2008). Complement component C1q inhibits beta-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpain-independent mechanisms. Journal of Neurochemistry, 104, 696–707.PubMed
go back to reference Podack, E. R., Tschoop, J., & Muller-Eberhard, H. J. (1982). Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b–8 assembly. Journal of Experimental Medicine, 156, 268–282.PubMed Podack, E. R., Tschoop, J., & Muller-Eberhard, H. J. (1982). Molecular organization of C9 within the membrane attack complex of complement. Induction of circular C9 polymerization by the C5b–8 assembly. Journal of Experimental Medicine, 156, 268–282.PubMed
go back to reference Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A. K., et al. (2006). Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO Journal, 25, 1364–1374.PubMed Rahpeymai, Y., Hietala, M. A., Wilhelmsson, U., Fotheringham, A., Davies, I., Nilsson, A. K., et al. (2006). Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO Journal, 25, 1364–1374.PubMed
go back to reference Reiman, R., Campos Torres, A., Martin, B. K., Ting, J. P., Campbell, I. L., & Barnum, S. R. (2005). Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis. Neuroscience Letters, 390, 134–138.PubMed Reiman, R., Campos Torres, A., Martin, B. K., Ting, J. P., Campbell, I. L., & Barnum, S. R. (2005). Expression of C5a in the brain does not exacerbate experimental autoimmune encephalomyelitis. Neuroscience Letters, 390, 134–138.PubMed
go back to reference Reiman, R., Gerard, C., Campbell, I. L., & Barnum, S. R. (2002). Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis. European Journal of Immunology, 32, 1157–1163.PubMed Reiman, R., Gerard, C., Campbell, I. L., & Barnum, S. R. (2002). Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis. European Journal of Immunology, 32, 1157–1163.PubMed
go back to reference Ricklin, D., & Lambris, J. D. (2007). Complement-targeted therapeutics. Nature Biotechnology, 25, 1265–1275.PubMed Ricklin, D., & Lambris, J. D. (2007). Complement-targeted therapeutics. Nature Biotechnology, 25, 1265–1275.PubMed
go back to reference Rittirsch, D., Flierl, M. A., Nadeau, B. A., Day, D. E., Huber-Lang, M., Mackay, C. R., et al. (2008). Functional roles for C5a receptors in sepsis. Nature Medicine, 14, 551–557.PubMed Rittirsch, D., Flierl, M. A., Nadeau, B. A., Day, D. E., Huber-Lang, M., Mackay, C. R., et al. (2008). Functional roles for C5a receptors in sepsis. Nature Medicine, 14, 551–557.PubMed
go back to reference Roestenberg, M., McCall, M., Mollnes, T. E., van Deuren, M., Sprong, T., Klasen, I., et al. (2007). Complement activation in experimental human malaria infection. Transactions of the Royal Society of Tropical Medicine and Hygiene, 101, 643–649.PubMed Roestenberg, M., McCall, M., Mollnes, T. E., van Deuren, M., Sprong, T., Klasen, I., et al. (2007). Complement activation in experimental human malaria infection. Transactions of the Royal Society of Tropical Medicine and Hygiene, 101, 643–649.PubMed
go back to reference Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nature Biotechnology, 25, 1256–1264.PubMed Rother, R. P., Rollins, S. A., Mojcik, C. F., Brodsky, R. A., & Bell, L. (2007). Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nature Biotechnology, 25, 1256–1264.PubMed
go back to reference Rus, H., Cudrici, C., & Niculescu, F. (2005). C5b–9 complement complex in autoimmune demyelination and multiple sclerosis: Dual role in neuroinflammation and neuroprotection. Annals of Medicine, 37, 97–104.PubMed Rus, H., Cudrici, C., & Niculescu, F. (2005). C5b–9 complement complex in autoimmune demyelination and multiple sclerosis: Dual role in neuroinflammation and neuroprotection. Annals of Medicine, 37, 97–104.PubMed
go back to reference Sayah, S., Ischenko, A. M., Zhakhov, A., Bonnard, A. S., & Fontaine, M. (1999). Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: Specific increase in interleukin-6 mRNA expression. Journal of Neurochemistry, 72, 2426–2436.PubMed Sayah, S., Ischenko, A. M., Zhakhov, A., Bonnard, A. S., & Fontaine, M. (1999). Expression of cytokines by human astrocytomas following stimulation by C3a and C5a anaphylatoxins: Specific increase in interleukin-6 mRNA expression. Journal of Neurochemistry, 72, 2426–2436.PubMed
go back to reference Schieferdecker, H. L., Rothermel, E., Timmermann, A., Gotze, O., & Jungermann, K. (1997). Anaphylatoxin C5a receptor mRNA is strongly expressed in Kupffer and stellate cells and weakly in sinusoidal endothelial cells but not in hepatocytes of normal rat liver. FEBS Letters, 406, 305–309.PubMed Schieferdecker, H. L., Rothermel, E., Timmermann, A., Gotze, O., & Jungermann, K. (1997). Anaphylatoxin C5a receptor mRNA is strongly expressed in Kupffer and stellate cells and weakly in sinusoidal endothelial cells but not in hepatocytes of normal rat liver. FEBS Letters, 406, 305–309.PubMed
go back to reference Scolding, N. J., Morgan, B. P., & Compston, D. A. (1998). The expression of complement regulatory proteins by adult human oligodendrocytes. Journal of Neuroimmunology, 84, 69–75.PubMed Scolding, N. J., Morgan, B. P., & Compston, D. A. (1998). The expression of complement regulatory proteins by adult human oligodendrocytes. Journal of Neuroimmunology, 84, 69–75.PubMed
go back to reference Sewell, D. L., Nacewicz, B., Liu, F., Macvilay, S., Erdei, A., Lambris, J. D., et al. (2004). Complement C3 and C5 play critical roles in traumatic brain cryoinjury: Blocking effects on neutrophil extravasation by C5a receptor antagonist. Journal of Neuroimmunology, 155, 55–63.PubMed Sewell, D. L., Nacewicz, B., Liu, F., Macvilay, S., Erdei, A., Lambris, J. D., et al. (2004). Complement C3 and C5 play critical roles in traumatic brain cryoinjury: Blocking effects on neutrophil extravasation by C5a receptor antagonist. Journal of Neuroimmunology, 155, 55–63.PubMed
go back to reference Shen, Y., Lue, L., Yang, L., Roher, A., Kuo, Y., Strohmeyer, R., et al. (2001). Complement activation by neurofibrillary tangles in Alzheimer’s disease. Neuroscience Letters, 305, 165–168.PubMed Shen, Y., Lue, L., Yang, L., Roher, A., Kuo, Y., Strohmeyer, R., et al. (2001). Complement activation by neurofibrillary tangles in Alzheimer’s disease. Neuroscience Letters, 305, 165–168.PubMed
go back to reference Singhrao, S. K., Neal, J. W., Morgan, B. P., & Gasque, P. (1999). Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Experimental Neurology, 159, 362–376.PubMed Singhrao, S. K., Neal, J. W., Morgan, B. P., & Gasque, P. (1999). Increased complement biosynthesis by microglia and complement activation on neurons in Huntington’s disease. Experimental Neurology, 159, 362–376.PubMed
go back to reference Singhrao, S. K., Neal, J. W., Rushmere, N. K., Morgan, B. P., & Gasque, P. (2000). Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. The American Journal of Pathology, 157, 905–918.PubMed Singhrao, S. K., Neal, J. W., Rushmere, N. K., Morgan, B. P., & Gasque, P. (2000). Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. The American Journal of Pathology, 157, 905–918.PubMed
go back to reference Stahel, P. F., & Barnum, S. R. (1997). Bacterial meningitis: Complement gene expression in the central nervous system. Immunopharmacology, 38, 65–72.PubMed Stahel, P. F., & Barnum, S. R. (1997). Bacterial meningitis: Complement gene expression in the central nervous system. Immunopharmacology, 38, 65–72.PubMed
go back to reference Stahel, P. F., Frei, K., Eugster, H. P., Fontana, A., Hummel, K. M., Wetsel, R. A., et al. (1997a). TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. Journal of Immunology, 159, 861–869. Stahel, P. F., Frei, K., Eugster, H. P., Fontana, A., Hummel, K. M., Wetsel, R. A., et al. (1997a). TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. Journal of Immunology, 159, 861–869.
go back to reference Stahel, P. F., Kariya, K., Shohami, E., Barnum, S. R., Eugster, H., Trentz, O., et al. (2000). Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. Journal of Neuroimmunology, 109, 164–172.PubMed Stahel, P. F., Kariya, K., Shohami, E., Barnum, S. R., Eugster, H., Trentz, O., et al. (2000). Intracerebral complement C5a receptor (CD88) expression is regulated by TNF and lymphotoxin-alpha following closed head injury in mice. Journal of Neuroimmunology, 109, 164–172.PubMed
go back to reference Stahel, P. F., Kossmann, T., Morganti-Kossmann, M. C., Hans, V. H., & Barnum, S. R. (1997b). Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Molecular Brain Research, 50, 205–212.PubMed Stahel, P. F., Kossmann, T., Morganti-Kossmann, M. C., Hans, V. H., & Barnum, S. R. (1997b). Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Molecular Brain Research, 50, 205–212.PubMed
go back to reference Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., et al. (2007). The classical complement cascade mediates CNS synapse elimination. Cell, 131, 1164–1178.PubMed Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., et al. (2007). The classical complement cascade mediates CNS synapse elimination. Cell, 131, 1164–1178.PubMed
go back to reference Storrs, S. B., Kolb, W. P., & Olson, M. S. (1983). C1q binding and C1 activation by various isolated cellular membranes. Journal of Immunology, 131, 416–422. Storrs, S. B., Kolb, W. P., & Olson, M. S. (1983). C1q binding and C1 activation by various isolated cellular membranes. Journal of Immunology, 131, 416–422.
go back to reference Tenner, A. J., Ziccardi, R. J., & Cooper, N. R. (1984). Antibody-independent C1 activation by E. coli. Journal of Immunology, 133, 886–891. Tenner, A. J., Ziccardi, R. J., & Cooper, N. R. (1984). Antibody-independent C1 activation by E. coli. Journal of Immunology, 133, 886–891.
go back to reference Thomas, A., Gasque, P., Vaudry, D., Gonzalez, B., & Fontaine, M. (2000). Expression of a complete and functional complement system by human neuronal cells in vitro. International Immunology, 12, 1015–1023.PubMed Thomas, A., Gasque, P., Vaudry, D., Gonzalez, B., & Fontaine, M. (2000). Expression of a complete and functional complement system by human neuronal cells in vitro. International Immunology, 12, 1015–1023.PubMed
go back to reference Van Beek, J., Bernaudin, M., Petit, E., Gasque, P., Nouvelot, A., MacKenzie, E. T., et al. (2000). Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal cerebral ischemia in the mouse. Experimental Neurology, 161, 373–382.PubMed Van Beek, J., Bernaudin, M., Petit, E., Gasque, P., Nouvelot, A., MacKenzie, E. T., et al. (2000). Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal cerebral ischemia in the mouse. Experimental Neurology, 161, 373–382.PubMed
go back to reference Van Beek, J., Elward, K., & Gasque, P. (2003). Activation of complement in the central nervous system: Roles in neurodegeneration and neuroprotection. Annals of the New York Academy of Sciences, 992, 56–71.PubMed Van Beek, J., Elward, K., & Gasque, P. (2003). Activation of complement in the central nervous system: Roles in neurodegeneration and neuroprotection. Annals of the New York Academy of Sciences, 992, 56–71.PubMed
go back to reference Van Beek, J., van Meurs, M., t Hart, B. A., Brok, H. P., Neal, J. W., Chatagner, A., et al. (2005). Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation. Journal of Immunology, 174, 2353–2365. Van Beek, J., van Meurs, M., t Hart, B. A., Brok, H. P., Neal, J. W., Chatagner, A., et al. (2005). Decay-accelerating factor (CD55) is expressed by neurons in response to chronic but not acute autoimmune central nervous system inflammation associated with complement activation. Journal of Immunology, 174, 2353–2365.
go back to reference Veerhuis, R., Janssen, I., De Groot, C. J., Van Muiswinkel, F. L., Hack, C. E., & Eikelenboom, P. (1999). Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor. Experimental Neurology, 160, 289–299. Veerhuis, R., Janssen, I., De Groot, C. J., Van Muiswinkel, F. L., Hack, C. E., & Eikelenboom, P. (1999). Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor. Experimental Neurology, 160, 289–299.
go back to reference Veerhuis, R., Janssen, I., Hoozemans, J. J., De Groot, C. J., Hack, C. E., & Eikelenboom, P. (1998). Complement C1-inhibitor expression in Alzheimer’s disease. Acta Neuropathologica, 96, 287–296.PubMed Veerhuis, R., Janssen, I., Hoozemans, J. J., De Groot, C. J., Hack, C. E., & Eikelenboom, P. (1998). Complement C1-inhibitor expression in Alzheimer’s disease. Acta Neuropathologica, 96, 287–296.PubMed
go back to reference Vergunst, C. E., Gerlag, D. M., Dinant, H., Schulz, L., Vinkenoog, M., Smeets, T. J., et al. (2007). Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford), 46, 1773–1778. Vergunst, C. E., Gerlag, D. M., Dinant, H., Schulz, L., Vinkenoog, M., Smeets, T. J., et al. (2007). Blocking the receptor for C5a in patients with rheumatoid arthritis does not reduce synovial inflammation. Rheumatology (Oxford), 46, 1773–1778.
go back to reference Walker, D. G., Kim, S. U., & McGeer, P. L. (1995a). Complement and cytokine gene expression in cultured microglial derived from postmortem human brains. Journal of Neuroscience Research, 40, 478–493.PubMed Walker, D. G., Kim, S. U., & McGeer, P. L. (1995a). Complement and cytokine gene expression in cultured microglial derived from postmortem human brains. Journal of Neuroscience Research, 40, 478–493.PubMed
go back to reference Walker, D. G., Kim, S. U., & McGeer, P. L. (1998). Expression of complement C4 and C9 genes by human astrocytes. Brain Research, 809, 31–38.PubMed Walker, D. G., Kim, S. U., & McGeer, P. L. (1998). Expression of complement C4 and C9 genes by human astrocytes. Brain Research, 809, 31–38.PubMed
go back to reference Walker, D. G., & McGeer, P. L. (1992). Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. Molecular Brain Research, 14, 109–116.PubMed Walker, D. G., & McGeer, P. L. (1992). Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. Molecular Brain Research, 14, 109–116.PubMed
go back to reference Walker, D. G., & McGeer, P. L. (1993). Complement gene expression in neuroblastoma and astrocytoma cell lines of human origin. Neuroscience Letters, 157, 99–102.PubMed Walker, D. G., & McGeer, P. L. (1993). Complement gene expression in neuroblastoma and astrocytoma cell lines of human origin. Neuroscience Letters, 157, 99–102.PubMed
go back to reference Walker, D. G., Yasuhara, O., Patston, P. A., McGeer, E. G., & McGeer, P. L. (1995b). Complement C1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease. Brain Research, 675, 75–82.PubMed Walker, D. G., Yasuhara, O., Patston, P. A., McGeer, E. G., & McGeer, P. L. (1995b). Complement C1 inhibitor is produced by brain tissue and is cleaved in Alzheimer disease. Brain Research, 675, 75–82.PubMed
go back to reference Webster, S., Lue, L. F., Brachova, L., Tenner, A. J., McGeer, P. L., Terai, K., et al. (1997). Molecular and cellular characterization of the membrane attack complex, C5b–9, in Alzheimer’s disease. Neurobiology of Aging, 18, 415–421.PubMed Webster, S., Lue, L. F., Brachova, L., Tenner, A. J., McGeer, P. L., Terai, K., et al. (1997). Molecular and cellular characterization of the membrane attack complex, C5b–9, in Alzheimer’s disease. Neurobiology of Aging, 18, 415–421.PubMed
go back to reference Woodruff, T. M., Costantini, K. J., Crane, J. W., Atkin, J. D., Monk, P. N., Taylor, S. M., et al. (2008a). The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. Journal of Immunology, 181, 8727–8734. Woodruff, T. M., Costantini, K. J., Crane, J. W., Atkin, J. D., Monk, P. N., Taylor, S. M., et al. (2008a). The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. Journal of Immunology, 181, 8727–8734.
go back to reference Woodruff, T. M., Costantini, K. J., Taylor, S. M., & Noakes, P. G. (2008b). Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors. Advances in Experimental Medicine and Biology, 632, 143–158.PubMed Woodruff, T. M., Costantini, K. J., Taylor, S. M., & Noakes, P. G. (2008b). Role of complement in motor neuron disease: Animal models and therapeutic potential of complement inhibitors. Advances in Experimental Medicine and Biology, 632, 143–158.PubMed
go back to reference Woodruff, T. M., Crane, J. W., Proctor, L. M., Buller, K. M., Shek, A. B., de Vos, K., et al. (2006a). Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB Journal, 20, 1407–1417.PubMed Woodruff, T. M., Crane, J. W., Proctor, L. M., Buller, K. M., Shek, A. B., de Vos, K., et al. (2006a). Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB Journal, 20, 1407–1417.PubMed
go back to reference Woodruff, T. M., Pollitt, S., Proctor, L. M., Stocks, S. Z., Manthey, H. D., Williams, H. M., et al. (2005). Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. Journal of Pharmacology and Experimental Therapeutics, 314, 811–817.PubMed Woodruff, T. M., Pollitt, S., Proctor, L. M., Stocks, S. Z., Manthey, H. D., Williams, H. M., et al. (2005). Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. Journal of Pharmacology and Experimental Therapeutics, 314, 811–817.PubMed
go back to reference Woodruff, T. M., Proctor, L. M., Strachan, A. J., & Taylor, S. M. (2006b). Complement factor 5a as a therapeutic target. Drug Future, 31, 325–334. Woodruff, T. M., Proctor, L. M., Strachan, A. J., & Taylor, S. M. (2006b). Complement factor 5a as a therapeutic target. Drug Future, 31, 325–334.
go back to reference Woodruff, T. M., Strachan, A. J., Dryburgh, N., Shiels, I. A., Reid, R. C., Fairlie, D. P., et al. (2002). Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis and Rheumatism, 46, 2476–2485.PubMed Woodruff, T. M., Strachan, A. J., Dryburgh, N., Shiels, I. A., Reid, R. C., Fairlie, D. P., et al. (2002). Antiarthritic activity of an orally active C5a receptor antagonist against antigen-induced monarticular arthritis in the rat. Arthritis and Rheumatism, 46, 2476–2485.PubMed
go back to reference Xi, G., Hua, Y., Keep, R. F., Younger, J. G., & Hoff, J. T. (2001). Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke, 32, 162–167.PubMed Xi, G., Hua, Y., Keep, R. F., Younger, J. G., & Hoff, J. T. (2001). Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke, 32, 162–167.PubMed
go back to reference Yang, C., Jones, J. L., & Barnum, S. R. (1993). Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes. Journal of Neuroimmunology, 47, 123–132.PubMed Yang, C., Jones, J. L., & Barnum, S. R. (1993). Expression of decay-accelerating factor (CD55), membrane cofactor protein (CD46) and CD59 in the human astroglioma cell line, D54-MG, and primary rat astrocytes. Journal of Neuroimmunology, 47, 123–132.PubMed
go back to reference Yao, J., Harvath, L., Gilbert, D. L., & Colton, C. A. (1990). Chemotaxis by a CNS macrophage, the microglia. Journal of Neuroscience Research, 27, 36–42.PubMed Yao, J., Harvath, L., Gilbert, D. L., & Colton, C. A. (1990). Chemotaxis by a CNS macrophage, the microglia. Journal of Neuroscience Research, 27, 36–42.PubMed
go back to reference Zajicek, J., Wing, M., Skepper, J., & Compston, A. (1995). Human oligodendrocytes are not sensitive to complement. A study of CD59 expression in the human central nervous system. Laboratory Investigation, 73, 128–138.PubMed Zajicek, J., Wing, M., Skepper, J., & Compston, A. (1995). Human oligodendrocytes are not sensitive to complement. A study of CD59 expression in the human central nervous system. Laboratory Investigation, 73, 128–138.PubMed
go back to reference Zhou, J., Fonseca, M. I., Pisalyaput, K., & Tenner, A. J. (2008). Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer’s disease. Journal of Neurochemistry, 106, 2080–2092.PubMed Zhou, J., Fonseca, M. I., Pisalyaput, K., & Tenner, A. J. (2008). Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer’s disease. Journal of Neurochemistry, 106, 2080–2092.PubMed
Metadata
Title
The Role of the Complement System and the Activation Fragment C5a in the Central Nervous System
Authors
Trent M. Woodruff
Rahasson R. Ager
Andrea J. Tenner
Peter G. Noakes
Stephen M. Taylor
Publication date
01-06-2010
Publisher
Humana Press Inc
Published in
NeuroMolecular Medicine / Issue 2/2010
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-009-8085-y

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