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Published in: Translational Stroke Research 1/2012

01-07-2012 | Original Article

Gr1+ Macrophages and Dendritic Cells Dominate the Inflammatory Infiltrate 12 h After Experimental Intracerebral Hemorrhage

Authors: Matthew D. Hammond, Youxi Ai, Lauren H. Sansing

Published in: Translational Stroke Research | Special Issue 1/2012

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Abstract

Intracerebral hemorrhage (ICH) is a devastating disease lacking an effective treatment. While the initial injury occurs within minutes, an inflammatory response contributes to ongoing tissue damage over hours to days. Relatively little is known about leukocyte trafficking into the brain in the hours after ICH onset. Understanding these events may lead to identification of new therapeutic targets. Using the blood injection mouse model of ICH, the numbers of leukocytes in the ipsilateral and contralateral brain were quantified by flow cytometry 12 h after surgery. Perihematomal inflammation was confirmed by histology and chemokines and cytokines in the brain quantified by multiplex ELISA. Few neutrophils were detected in the brain 12 h after ICH. The majority of leukocytes consisted of inflammatory macrophages (CD45.1hiCD3Ly6GCD11cCD11b+Gr1+ cells) and inflammatory dendritic cells (CD45.1hiCD3Ly6GCD11cintCD11b+Gr1+ cells). Microglia numbers did not differ between the hemispheres. These results indicate that blood-derived monocyte populations traffic into brain early after ICH and outnumber neutrophils at 12 h.
Literature
1.
2.
go back to reference Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27:894–908.PubMedCrossRef Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2007;27:894–908.PubMedCrossRef
3.
go back to reference Kane PJ, Modha P, Strachan RD, Cook S, Chambers IR, Clayton CB, et al. The effect of immunosuppression on the development of cerebral oedema in an experimental model of intracerebral haemorrhage: whole body and regional irradiation. J Neurol Neurosurg Psychiatry. 1992;55:781–6.PubMedCrossRef Kane PJ, Modha P, Strachan RD, Cook S, Chambers IR, Clayton CB, et al. The effect of immunosuppression on the development of cerebral oedema in an experimental model of intracerebral haemorrhage: whole body and regional irradiation. J Neurol Neurosurg Psychiatry. 1992;55:781–6.PubMedCrossRef
4.
go back to reference Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain. 2008;131:616–29.PubMedCrossRef Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain. 2008;131:616–29.PubMedCrossRef
6.
go back to reference Del Bigio MR, Yan H-J, Buist R, Peeling J, del Zoppo GJ. Experimental intracerebral hemorrhage in rats: magnetic resonance imaging and histopathological correlates. Stroke. 1996;27:2312–20.PubMedCrossRef Del Bigio MR, Yan H-J, Buist R, Peeling J, del Zoppo GJ. Experimental intracerebral hemorrhage in rats: magnetic resonance imaging and histopathological correlates. Stroke. 1996;27:2312–20.PubMedCrossRef
7.
go back to reference Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci Lett. 2000;283:230–2.PubMedCrossRef Xue M, Del Bigio MR. Intracerebral injection of autologous whole blood in rats: time course of inflammation and cell death. Neurosci Lett. 2000;283:230–2.PubMedCrossRef
8.
go back to reference Gong C, Hoff JT, Keep RF. Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res. 2000;871:57–65.PubMedCrossRef Gong C, Hoff JT, Keep RF. Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res. 2000;871:57–65.PubMedCrossRef
9.
go back to reference Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669–92.PubMedCrossRef Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009;27:669–92.PubMedCrossRef
10.
go back to reference Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. Tnf/inos-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity. 2003;19:59–70.PubMedCrossRef Serbina NV, Salazar-Mather TP, Biron CA, Kuziel WA, Pamer EG. Tnf/inos-producing dendritic cells mediate innate immune defense against bacterial infection. Immunity. 2003;19:59–70.PubMedCrossRef
11.
go back to reference King IL, Dickendesher TL, Segal BM. Circulating ly-6c + myeloid precursors migrate to the cns and play a pathogenic role during autoimmune demyelinating disease. Blood. 2009;113:3190–7.PubMedCrossRef King IL, Dickendesher TL, Segal BM. Circulating ly-6c + myeloid precursors migrate to the cns and play a pathogenic role during autoimmune demyelinating disease. Blood. 2009;113:3190–7.PubMedCrossRef
12.
go back to reference Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV. Absence of the chemokine receptor ccr2 protects against cerebral ischemia/reperfusion injury in mice. Stroke. 2007;38:1345–53.PubMedCrossRef Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV. Absence of the chemokine receptor ccr2 protects against cerebral ischemia/reperfusion injury in mice. Stroke. 2007;38:1345–53.PubMedCrossRef
13.
go back to reference Schilling M, Strecker JK, Ringelstein EB, Schabitz WR, Kiefer R. The role of cc chemokine receptor 2 on microglia activation and blood-borne cell recruitment after transient focal cerebral ischemia in mice. Brain Res. 2009;1289:79–84.PubMedCrossRef Schilling M, Strecker JK, Ringelstein EB, Schabitz WR, Kiefer R. The role of cc chemokine receptor 2 on microglia activation and blood-borne cell recruitment after transient focal cerebral ischemia in mice. Brain Res. 2009;1289:79–84.PubMedCrossRef
14.
go back to reference Yao Y, Tsirka SE. The CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage. Glia. 2012;60(6):908–18.PubMedCrossRef Yao Y, Tsirka SE. The CCL2-CCR2 system affects the progression and clearance of intracerebral hemorrhage. Glia. 2012;60(6):908–18.PubMedCrossRef
15.
go back to reference Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007;317:666–70.PubMedCrossRef Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007;317:666–70.PubMedCrossRef
16.
go back to reference Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037–47.PubMedCrossRef Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037–47.PubMedCrossRef
17.
go back to reference Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177:7303–11.PubMed Martinez FO, Gordon S, Locati M, Mantovani A. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006;177:7303–11.PubMed
18.
go back to reference Nakano H, Lin KL, Yanagita M, Charbonneau C, Cook DN, Kakiuchi T, et al. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute t helper type 1 immune responses. Nat Immunol. 2009;10:394–402.PubMedCrossRef Nakano H, Lin KL, Yanagita M, Charbonneau C, Cook DN, Kakiuchi T, et al. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute t helper type 1 immune responses. Nat Immunol. 2009;10:394–402.PubMedCrossRef
19.
go back to reference Anzai A, Anzai T, Nagai S, Maekawa Y, Naito K, Kaneko H, et al. Regulatory role of dendritic cells in post-infarction healing and left ventricular remodeling. Circulation. 2012;125(10):1234–45.PubMedCrossRef Anzai A, Anzai T, Nagai S, Maekawa Y, Naito K, Kaneko H, et al. Regulatory role of dendritic cells in post-infarction healing and left ventricular remodeling. Circulation. 2012;125(10):1234–45.PubMedCrossRef
20.
go back to reference Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K. Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol. 2011;70:646–56.PubMedCrossRef Sansing LH, Harris TH, Welsh FA, Kasner SE, Hunter CA, Kariko K. Toll-like receptor 4 contributes to poor outcome after intracerebral hemorrhage. Ann Neurol. 2011;70:646–56.PubMedCrossRef
21.
go back to reference Sagar D, Foss C, El Baz R, Pomper MG, Khan ZK, Jain P. Mechanisms of dendritic cell trafficking across the blood–brain barrier. J Neuroimmune Pharmacol. 2012;7(1):74–94.PubMedCrossRef Sagar D, Foss C, El Baz R, Pomper MG, Khan ZK, Jain P. Mechanisms of dendritic cell trafficking across the blood–brain barrier. J Neuroimmune Pharmacol. 2012;7(1):74–94.PubMedCrossRef
22.
go back to reference Xi G, Hua Y, Keep RF, Younger JG, Hoff JT. Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke. 2001;32:162–7.PubMedCrossRef Xi G, Hua Y, Keep RF, Younger JG, Hoff JT. Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke. 2001;32:162–7.PubMedCrossRef
23.
go back to reference Hua Y, Wu J, Keep RF, Nakamura T, Hoff JT, Xi G. Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation. Neurosurgery. 2006;58:542–50. discussion 542–550.PubMed Hua Y, Wu J, Keep RF, Nakamura T, Hoff JT, Xi G. Tumor necrosis factor-alpha increases in the brain after intracerebral hemorrhage and thrombin stimulation. Neurosurgery. 2006;58:542–50. discussion 542–550.PubMed
24.
go back to reference Mayne M, Ni W, Yan HJ, Xue M, Johnston JB, Del Bigio MR, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage. Stroke. 2001;32:240–8.PubMedCrossRef Mayne M, Ni W, Yan HJ, Xue M, Johnston JB, Del Bigio MR, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage. Stroke. 2001;32:240–8.PubMedCrossRef
25.
go back to reference Liesz A, Middelhoff M, Zhou W, Karcher S, Illanes S, Veltkamp R. Comparison of humoral neuroinflammation and adhesion molecule expression in two models of experimental intracerebral hemorrhage. Exp Transl Stroke Med. 2011;3:11.PubMedCrossRef Liesz A, Middelhoff M, Zhou W, Karcher S, Illanes S, Veltkamp R. Comparison of humoral neuroinflammation and adhesion molecule expression in two models of experimental intracerebral hemorrhage. Exp Transl Stroke Med. 2011;3:11.PubMedCrossRef
26.
go back to reference Carmichael ST, Vespa PM, Saver JL, Coppola G, Geschwind DH, Starkman S, et al. Genomic profiles of damage and protection in human intracerebral hemorrhage. J Cereb Blood Flow Metab. 2008;28:1860–75.PubMedCrossRef Carmichael ST, Vespa PM, Saver JL, Coppola G, Geschwind DH, Starkman S, et al. Genomic profiles of damage and protection in human intracerebral hemorrhage. J Cereb Blood Flow Metab. 2008;28:1860–75.PubMedCrossRef
27.
go back to reference Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol. 2004;75:388–97.PubMedCrossRef Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol. 2004;75:388–97.PubMedCrossRef
28.
go back to reference Renno T, Krakowski M, Piccirillo C, Lin JY, Owens T. Tnf-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by th1 cytokines. J Immunol. 1995;154:944–53.PubMed Renno T, Krakowski M, Piccirillo C, Lin JY, Owens T. Tnf-alpha expression by resident microglia and infiltrating leukocytes in the central nervous system of mice with experimental allergic encephalomyelitis. Regulation by th1 cytokines. J Immunol. 1995;154:944–53.PubMed
29.
go back to reference Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–89.PubMedCrossRef Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–89.PubMedCrossRef
Metadata
Title
Gr1+ Macrophages and Dendritic Cells Dominate the Inflammatory Infiltrate 12 h After Experimental Intracerebral Hemorrhage
Authors
Matthew D. Hammond
Youxi Ai
Lauren H. Sansing
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Translational Stroke Research / Issue Special Issue 1/2012
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-012-0174-9

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