Top

Journal of Neuroinflammation

Published in:

Open Access 01-12-2010 | Research

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Authors: Ying Wang, Yansong Li, Shawn L Dalle Lucca, Milomir Simovic, George C Tsokos, Jurandir J Dalle Lucca

Published in: Journal of Neuroinflammation | Issue 1/2010

Abstract

Background

Activated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.

Methods

Cultured primary cortical neurons from embryonic Sprague-Dawley rats were assigned one of four groups: control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ng/ml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectively regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src.

Results

When compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. Furthermore, treatment with DAF resulted in decreased accumulation of C3a, MAC, C3a-C3aR interaction, caspase-9, activated caspase-3, and pTyr416-Src (activated Src) tyrosine kinase.

Conclusion

DAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. This study supports the inhibiting of complement as a neuroprotective strategy against CNS ischemia/reperfusion injury.

Available only for authorised users

Clarkson AN, Sutherland BA, Appleton I: The biology and pathology of hypoxia-ischemia: an update. Arch Immunol Ther Exp. 2005, 53: 213-25.

Fujikawa DG: Confusion between neuronal apoptosis and activation of programmed cell death mechanisms in acute necrotic insults. Trends Neurosci. 2000, 23: 410-411. 10.1016/S0166-2236(00)01601-5.CrossRefPubMed

Fleming S: Complement Inhibitors in Trauma From: Combat Medicine: Basic and Clinical Research in Military Trauma and Emergency Medicine. 2003, Humana Press, Inc., Towtoaw, NJ

Arumugam TV, Woodruff TM, Lathia JD, Selvaraj PK, Mattson MP, Taylor SM: Neuropretection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience. 2009, 158: 1074-1089. 10.1016/j.neuroscience.2008.07.015.PubMedCentralCrossRefPubMed

Czurko A, Nishino H: Appearance of immunoglobulin G and complement factor C3 in the striatum after transient focal ischemia in the rat. Neurosci Lett. 1994, 166: 51-54. 10.1016/0304-3940(94)90838-9.CrossRefPubMed

Lindsberg PJ, Ohman J, Lehto T, Karjalainen-Lindsberg ML, Paetau A, Wuorimaa T, Carpen O, Kaste M, Meri S: Complement activation in the central nervous system following blood-brain barrier damage in man. Ann Neurol. 1996, 40: 587-596. 10.1002/ana.410400408.CrossRefPubMed

Barnum SR: Complement biosynthesis in the central nervous system. Crit Rev Oral Biol Med. 1995, 6: 132-146. 10.1177/10454411950060020301.CrossRefPubMed

Gasque P, Fontaine M, Morgan BP: Complement expression in human brain. Biosynthesis of terminal pathway components and regulators in human glial cells and cell lines. J Immunol. 1995, 154: 4726-4733.PubMed

Bellander BM, Singhrao SK, Ohlsson M, Mattsson P, Svensson M: Complement activation in the human brain after traumatic head injury. J Neurotrauma. 2001, 18: 1295-1311. 10.1089/08977150152725605.CrossRefPubMed

10.

Singhrao SK, Neal JW, Rushmere NK, Morgan BP, Gasque P: Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am J Pathol. 2000, 157: 905-918.PubMedCentralCrossRefPubMed

11.

Leinhase I, Schmidt OI, Thurman JM, Hossini AM, Rozanski M, Taha ME, Scheffler A, John T, Smith WR, Holers VM, Stahel PF: Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp Neurol. 2006, 199: 454-464. 10.1016/j.expneurol.2006.01.033.CrossRefPubMed

12.

Leinhase I, Rozanski M, Harhausen D, Thurman JM, Schmidt OI, Hossini AM, Taha ME, Rittirsch D, Ward PA, Holers VM, Ertel W, Stahel PF: Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice. J Neuroinflammation. 2007, 4: 13-25. 10.1186/1742-2094-4-13.PubMedCentralCrossRefPubMed

13.

Lublin DM, Atkinson JP: Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989, 7: 35-58. 10.1146/annurev.iy.07.040189.000343.CrossRefPubMed

14.

Pedersen ED, Froyland E, Kvissel AK, Pharo AM, Skalhegg BS, Rootwelt T, Mollnes TE: Expression of complement regulators and receptors on human NT2-N neurons--effect of hypoxia and reoxygenation. Mol Immunol. 2007, 44: 2459-2468. 10.1016/j.molimm.2006.10.022.CrossRefPubMed

15.

VanLandingham JW, Cekic M, Cutler S, Hoffman SW, Stein DG: Neurosteroids reduce inflammation after TBI through DAF induction. Neurosci Lett. 2007, 425: 94-98. 10.1016/j.neulet.2007.08.045.PubMedCentralCrossRefPubMed

16.

Weeks C, Moratz C, Zacharia A, Stracener C, Egan R, Peckham R, Moore FD, Tsokos GC: Decay-accelerating factor attenuates remote ischemia-reperfusion-initiated organ damage. Clin Immunol. 2007, 124: 311-327. 10.1016/j.clim.2007.05.010.CrossRefPubMed

17.

Prabhakaran K, Li L, Borowitz JL, Isom GE: Cyanide induces different modes of death in cortical and mesencephalon cells. J Pharmacol Exp Ther. 2002, 303: 510-519. 10.1124/jpet.102.039453.CrossRefPubMed

18.

Harris CL, Spiller OB, Morgan BP: Human and rodent decay-accelerating factors (CD55) are not species restricted in their complement-inhibiting activities. Immunology. 2000, 100: 462-470. 10.1046/j.1365-2567.2000.00066.x.PubMedCentralCrossRefPubMed

19.

Tavakoli-Far B, Rahbar-Roshandel N, Rahimi-Moghaddam P, Mahmoudian M: Neuroprotective effects of mebudipine and dibudipine on cerebral oxygen-glucose deprivation/reperfusion injury. Eur J Pharmacol. 2009, 610: 12-17. 10.1016/j.ejphar.2009.03.017.CrossRefPubMed

20.

Hering H, Sheng M: Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci. 2001, 2: 880-888. 10.1038/35104061.CrossRefPubMed

21.

Mills EM, Gunasekar P, Borowitz JL, Isom GE: Differential susceptibility of brain areas to cyanide involves different modes of cell death. Toxicol Appl Pharmacol. 1999, 156: 6-16. 10.1006/taap.1999.8630.CrossRefPubMed

22.

Soriano P, Montgomery C, Geske R, Bradley A: Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991, 64: 693-702. 10.1016/0092-8674(91)90499-O.CrossRefPubMed

23.

Paul R, Zhang ZG, Eliceiri BP, Jiang Q, Boccia AD, Zhang RL, Chopp M, Cheresh DA: Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med. 2001, 7: 222-227. 10.1038/84675.CrossRefPubMed

24.

Lennmyr F, Ericsson A, Gerwins P, Akterin S, Ahlstrom H, Terent A: Src family kinase-inhibitor PP2 reduces focal ischemic brain injury. Acta Neurol Scand. 2004, 110: 175-179. 10.1111/j.1600-0404.2004.00306.x.CrossRefPubMed

25.

Eckstein M: Enhancing public health preparedness for a terrorist attack involving cyanide. J Emerg Med. 2008, 35: 59-65. 10.1016/j.jemermed.2007.03.040.CrossRefPubMed

26.

Kanthasamy AG, Borowitz JL, Pavlakovic G, Isom GE: Dopaminergic neurotoxicity of cyanide: neurochemical, histological and behavioral characterization. Toxicol Appl Pharmacol. 1994, 126: 156-163. 10.1006/taap.1994.1102.CrossRefPubMed

27.

Hutter-Paier B, Grygar E, Loibner M, Skofitsch G, Windisch M: Effects of NaCN and ionomycin on neuronal viability and on the abundance of microtubule-associated proteins MAP1, MAP2, and tau in isolated chick cortical neurons. Cell Tissue Res. 2000, 302: 39-47. 10.1007/s004410000258.CrossRefPubMed

28.

D'Agostino D, Mazza E, Neubauer JA: Heme Oxygenase Is Necessary for the Excitatory Response of Cultured Neonatal Rat Rostral Ventrolateral Medulla Neurons to Hypoxia. Am J Physiol Regul Integr Comp Physiol. 2009, 296: 102-18.CrossRef

29.

Krieglstein J, Brungs H, Peruche B: Cultured neurons for testing cerebroprotective drug effects in vitro. J Pharmacol Methods. 1988, 20: 39-46. 10.1016/0160-5402(88)90014-9.CrossRefPubMed

30.

Nieber K: Hypoxia and neuronal function under in vitro conditions. Pharmacol Ther. 1999, 82: 71-86. 10.1016/S0163-7258(98)00061-8.CrossRefPubMed

31.

Moody WJ, Bosma MM: Ion channel development, spontaneous activity, and activity-dependent development in nerve and muscle cells. Physiol Rev. 2005, 85: 883-941. 10.1152/physrev.00017.2004.CrossRefPubMed

32.

Fiala JC, Spacek J, Harris KM: Dendritic spine pathology: cause or consequence of neurological disorders?. Brain Res Brain Res Rev. 2002, 39: 29-54. 10.1016/S0165-0173(02)00158-3.CrossRefPubMed

33.

Penzes P, Beeser A, Chernoff J, Schiller MR, Eipper BA, Mains RE, Huganir RL: Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron. 2003, 37: 263-274. 10.1016/S0896-6273(02)01168-6.CrossRefPubMed

34.

Brown CE, Wong C, Murphy TH: Rapid morphologic plasticity of peri-infarct dendritic spines after focal ischemic stroke. Stroke. 2008, 39: 1286-1291. 10.1161/STROKEAHA.107.498238.CrossRefPubMed

35.

Bossenmeyer C, Chihab R, Muller S, Schroeder H, Daval JL: Hypoxia/reoxygenation induces apoptosis through biphasic induction of protein synthesis in cultured rat brain neurons. Brain Res. 1998, 787: 107-116. 10.1016/S0006-8993(97)01527-8.CrossRefPubMed

36.

Mikesch JH, Buerger H, Simon R, Brandt B: Decay-accelerating factor (CD55): a versatile acting molecule in human malignancies. Biochim Biophys Acta. 2006, 1766: 42-52.PubMed

37.

Jones J, Morgan BP: Apoptosis is associated with reduced expression of complement regulatory molecules, adhesion molecules and other receptors on polymorphonuclear leucocytes: functional relevance and role in inflammation. Immunology. 1995, 86: 651-60.PubMedCentralPubMed

38.

Shenoy-Scaria AM, Kwong J, Fujita T, Olszowy MW, Shaw AS, Lublin DM: Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1. J Immunol. 1992, 149: 3535-41.PubMed

39.

Liu Y, Zhang G, Gao C, Hou X: NMDA receptor activation results in tyrosine phosphorylation of NMDA receptor subunit 2A(NR2A) and interaction of Pyk2 and Src with NR2A after transient cerebral ischemia and reperfusion. Brain Res. 2001, 909: 51-8. 10.1016/S0006-8993(01)02619-1.CrossRefPubMed

40.

Jadhav V, Matchett G, Hsu FP, Zhang JH: Inhibition of Src tyrosine kinase and effect on outcomes in a new in vivo model of surgically induced brain injury. J Neurosurg. 2007, 106: 680-686. 10.3171/jns.2007.106.4.680.CrossRefPubMed

41.

Salter MW, Kalia LV: Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci. 2004, 5: 317-28. 10.1038/nrn1368.CrossRefPubMed

42.

Van Beek J, Bernaudin M, Petit E, Gasque P, Nouvelot A, Mackenzie ET, Fontaine M: Expression of receptors for complement anaphylatoxins C3a and C5a following permanent focal ischemia in the mouse. Experimental Neurology. 2000, 161: 373-382. 10.1006/exnr.1999.7273.CrossRefPubMed

43.

Ischenko A, Sayah S, Patte C, Andreev S, Gasque P, Schouft MT, Vaudry H, Fontaine M: Expression of a functional anaphylatoxin C3a receptor by astrocytes. J Neurochem. 1998, 71: 2487-2496.CrossRefPubMed

44.

Li K, Anderson KJ, Peng Q, Noble A, Lu B, Kelly AP, Wang N, Sacks SH, Zhou W: Cyclic AMP plays a critical role in C3a-receptor-mediated regulation of dendritic cells in antigen uptake and T-cell stimulation. Blood. 2008, 112: 5084-5094. 10.1182/blood-2008-05-156646.CrossRefPubMed

45.

Strainic MG, Liu J, Huang D, An F, Lalli PN, Muqim N, Shapiro VS, Dubyak GR, Heeger PS, Medof ME: Locally Produced Complement Fragments C5a and C3a Provide Both Costimulatory and Survival Signals to Naive CD4⁺ T Cells. Immunity. 2008, 28: 425-4353. 10.1016/j.immuni.2008.02.001.PubMedCentralCrossRefPubMed

46.

Fosbrink M, Niculescu F, Rus H: The role of c5b-9 terminal complement complex in activation of the cell cycle and transcription. Immunol Res. 2005, 31: 37-46. 10.1385/IR:31:1:37.CrossRefPubMed

47.

Morgan BP, Gasque P, Singhrao SK, Piddlesden SJ: Role of complement in inflammation and injury in the nervous system. Exp Clin Immunogenet. 1997, 14: 19-23.PubMed

48.

Stahel PF, Morganti-Kossmann MC, Perez D, Redaelli C, Gloor B, Trentz O, Kossmann T: Intrathecal levels of complement-derived soluble membrane attack complex (sC5b-9) correlate with blood-brain barrier dysfunction in patients with traumatic brain injury. J Neurotrauma. 2001, 18: 773-781. 10.1089/089771501316919139.CrossRefPubMed

49.

Hensel F, Hermann R, Schubert C, Abe N, Schmidt K, Franke A, Shevchenko A, Mann M, Muller-Hermelink HK, Vollmers HP: Characterization of glycosylphosphatidylinositol-linked molecule (CD55/decay-accelerating factor as the receptor for antibody SC-1-induced apoptosis. Cancer Res. 1999, 59: 5299-306.PubMed

50.

Nauta AJ, Daha MR, Tijsma O, Water van de B, Tedesco F, Roos A: The membrane attack complex of complement induces caspase activation and apoptosis. Eur J Immunol. 2002, 32: 783-792. 10.1002/1521-4141(200203)32:3<783::AID-IMMU783>3.0.CO;2-Q.CrossRefPubMed

51.

Ziporen L, Donin N, Shmushkovich T, Gross A, Fishelson Z: Programmed necrotic cell death induced by complement involves a Bid-dependent pathway. J Immunol. 2009, 182: 515-521.CrossRefPubMed

52.

Takagi N, Cheung HH, Bissoon N, Teves L, Wallace MC, Gurd JW: The effect of transient global ischemia on the interaction of Src and Fyn with the N-methyl-D-aspartate receptor and postsynaptic densities: possible involvement of Src homology 2 domains. J Cereb Blood Flow Metab. 1999, 19: 880-888. 10.1097/00004647-199908000-00007.CrossRefPubMed

53.

Cheung HH, Teves L, Wallace MC, Gurd JW: Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the N-methyl-d-aspartate receptor. J Neurochem. 2003, 86: 1441-1449. 10.1046/j.1471-4159.2003.01951.x.CrossRefPubMed

Title: Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury
Authors: Ying Wang
Yansong Li
Shawn L Dalle Lucca
Milomir Simovic
George C Tsokos
Jurandir J Dalle Lucca
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2010
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-7-24

At a glance: The STEP trials

Springer Medicine

Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury

Abstract

Background

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2010

Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury

Phagocytosis and LPS alter the maturation state of β-amyloid precursor protein and induce different Aβ peptide release signatures in human mononuclear phagocytes

β-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices

Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Distinct modulation of microglial amyloid β phagocytosis and migration by neuropeptidesi

PSAPP mice exhibit regionally selective reductions in gliosis and plaque deposition in response to S100B ablation