Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

Frontiers in Cellular Neuroscience

Volumn 8, Issue November, 2014, Pages

  Orsini, Franca ^a   De Blasio, Daiana ^a,b   Zangari, Rosalia ^a,c   Zanier, Elisa R ^a   De Simoni, Maria Grazia ^a  

^a MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^b UNIVERSITY OF CHIETI   (Italy)

^c UNIVERSITY OF MILAN   (Italy)

Author keywords

Alzheimer s disease; Brain homeostasis; Complement system; Endothelium; Stroke; Therapeutic targets; Traumatic brain injury

Indexed keywords

AMYLOID BETA PROTEIN; ANAPHYLATOXIN; ARGININE CARBOXYPEPTIDASE; C REACTIVE PROTEIN; CD59 ANTIGEN; COBROTOXIN; COLLECTIN; COMPLEMENT COMPONENT C3B RECEPTOR; COMPLEMENT COMPONENT C4 BINDING PROTEIN; COMPLEMENT FACTOR H; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DECAY ACCELERATING FACTOR; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; FICOLIN; G PROTEIN COUPLED RECEPTOR KINASE 6; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 1BETA; INTERLEUKIN 6; INTERLEUKIN 8; MANNAN BINDING LECTIN ASSOCIATED SERINE PROTEASE; MEMBRANE COFACTOR PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE P38; MONOCYTE CHEMOTACTIC PROTEIN 1; OPSONIN; PROTEINASE ACTIVATED RECEPTOR; RANTES; SERINE PROTEINASE; THROMBIN; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BLOOD BRAIN BARRIER; BRAIN HOMEOSTASIS; BRAIN INJURY; CELL SURVIVAL; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM; DEGENERATIVE DISEASE; GENE EXPRESSION; HOMEOSTASIS; HUMAN; IMMUNOCOMPETENCE; IMMUNOSURVEILLANCE; INNATE IMMUNITY; MAJOR HISTOCOMPATIBILITY COMPLEX; MAJOR HISTOCOMPATIBILITY COMPLEX 1; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVE REGENERATION; NERVOUS SYSTEM DEVELOPMENT; NERVOUS SYSTEM INFLAMMATION; NEUROTOXICITY; NONHUMAN; PARKINSON DISEASE; RETINA GANGLION CELL; REVIEW; SUBARACHNOID HEMORRHAGE; SYNAPTIC POTENTIAL;

EID: 84926467444     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00380     Document Type: Review

References (176)

1. Ager, R. R., Fonseca, M. I., Chu, S.-H., Sanderson, S. D., Taylor, S. M., Woodruff, T. M., et al. (2010). Microglial C5aR (CD88) expression correlates with amyloid-beta deposition in murine models of Alzheimer's disease. J. Neurochem. 113, 389-401. doi: 10.1111/j.1471-4159.2010.06595.x.
2. Akita, N., Nakase, H., Kaido, T., Kanemoto, Y., and Sakaki, T. (2003). Protective effect of C1 esterase inhibitor on reperfusion injury in the rat middle cerebral artery occlusion model. Neurosurgery 52, 395-400; discussion 400-401. doi: 10.1227/01.neu.0000043710.61233.b4.
3. Alexander, J. J., Anderson, A. J., Barnum, S. R., Stevens, B., and Tenner, A. J. (2008). The complement cascade: Yin-Yang in neuroinflammation-neuro-protection and-degeneration. J. Neurochem. 107, 1169-1187. doi: 10.1111/j.1471-4159.2008.05668.x.
4. Amara, U., Flierl, M. A., Rittirsch, D., Klos, A., Chen, H., Acker, B., et al. (2010). Molecular intercommunication between the complement and coagulation systems. J. Immunol. 185, 5628-5636. doi: 10.4049/jimmunol.0903678.
5. Arumugam, T. V., Tang, S.-C., Lathia, J. D., Cheng, A., Mughal, M. R., Chigurupati, S., et al. (2007). Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc. Natl. Acad. Sci. U S A 104, 14104-14109. doi: 10.1073/pnas.0700506104.
6. Arumugam, T. V., Woodruff, T. M., Lathia, J. D., Selvaraj, P. K., Mattson, M. P., and Taylor, S. M. (2009). Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 158, 1074-1089. doi: 10.1016/j.neuroscience.2008.07.015.
7. Atkinson, C., Zhu, H., Qiao, F., Varela, J. C., Yu, J., Song, H., et al. (2006). Complement-dependent P-selectin expression and injury following ischemic stroke. J. Immunol. 177, 7266-7274. doi: 10.4049/jimmunol.177.10.7266.
8. Barnum, S. R., Ames, R. S., Maycox, P. R., Hadingham, S. J., Meakin, J., Harrison, D., et al. (2002). Expression of the complement C3a and C5a receptors after permanent focal ischemia: an alternative interpretation. Glia 38, 169-173. doi: 10.1002/glia.10069.
9. Bellander, B. M., Singhrao, S. K., Ohlsson, M., Mattsson, P., and Svensson, M. (2001). Complement activation in the human brain after traumatic head injury. J. Neurotrauma 18, 1295-1311. doi: 10.1089/08977150152725605.
10. Bellavance, M.-A., and Rivest, S. (2012). The neuroendocrine control of the innate immune system in health and brain diseases. Immunol. Rev. 248, 36-55. doi: 10.1111/j.1600-065x.2012.01129.x.
11. Benoit, M. E., Hernandez, M. X., Dinh, M. L., Benavente, F., Vasquez, O., and Tenner, A. J. (2013). C1q-induced LRP1B and GPR6 proteins expressed early in Alzheimer disease mouse models, are essential for the C1q-mediated protection against amyloid-β neurotoxicity. J. Biol. Chem. 288, 654-665. doi: 10.1074/jbc.M112.400168.
12. Benoit, M. E., and Tenner, A. J. (2011). Complement protein C1q-mediated neuroprotection is correlated with regulation of neuronal gene and microRNA expression. J. Neurosci. 31, 3459-3469. doi: 10.1523/JNEUROSCI.3932-10.2011.
13. Bialas, A. R., and Stevens, B. (2013). TGF-β signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat. Neurosci. 16, 1773-1782. doi: 10.1038/nn.3560.
14. Bjartmar, L., Huberman, A. D., Ullian, E. M., Rentería, R. C., Liu, X., Xu, W., et al. (2006). Neuronal pentraxins mediate synaptic refinement in the developing visual system. J. Neurosci. 26, 6269-6281. doi: 10.1523/jneurosci.4212-05.2006.
15. Bossi, F., Bulla, R., and Tedesco, F. (2008). Endothelial cells are a target of both complement and kinin system. Int. Immunopharmacol. 8, 143-147. doi: 10.1016/j.intimp.2007.08.006.
16. Bossi, F., Fischetti, F., Pellis, V., Bulla, R., Ferrero, E., Mollnes, T. E., et al. (2004). Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex. J. Immunol. 173, 6921-6927. doi: 10.4049/jimmunol.173.11.6921.
17. Bossi, F., Peerschke, E. I., Ghebrehiwet, B., and Tedesco, F. (2011). Cross-talk between the complement and the kinin system in vascular permeability. Immunol. Lett. 140, 7-13. doi: 10.1016/j.imlet.2011.06.006.
18. Brennan, F. H., Anderson, A. J., Taylor, S. M., Woodruff, T. M., and Ruitenberg, M. J. (2012). Complement activation in the injured central nervous system: another dual-edged sword? J. Neuroinflammation 9:137. doi: 10.1186/1742-2094-9-137.
19. Buchner, H. (1981). Centr Bakteriol Parasitenk. Zur. Nomenkl. Schutzenden Eiweisskorper 10, 699-701.
20. Burke, J. F., Stulc, J. L., Skolarus, L. E., Sears, E. D., Zahuranec, D. B., and Morgenstern, L. B. (2013). Traumatic brain injury may be an independent risk factor for stroke. Neurology 81, 33-39. doi: 10.1212/WNL.0b013e318297eecf.
21. Castellano, G., Melchiorre, R., Loverre, A., Ditonno, P., Montinaro, V., Rossini, M., et al. (2010). Therapeutic targeting of classical and lectin pathways of complement protects from ischemia-reperfusion-induced renal damage. Am. J. Pathol. 176, 1648-1659. doi: 10.2353/ajpath.2010.090276.
22. Cervera, A., Planas, A. M., Justicia, C., Urra, X., Jensenius, J. C., Torres, F., et al. (2010). Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PLoS One 5:e8433. doi: 10.1371/journal.pone.0008433.
23. Chamorro, Á., Meisel, A., Planas, A. M., Urra, X., van de Beek, D., and Veltkamp, R. (2012). The immunology of acute stroke. Nat. Rev. Neurol. 8, 401-410. doi: 10.1038/nrneurol.2012.98.
24. Chiu, I. M., Phatnani, H., Kuligowski, M., Tapia, J. C., Carrasco, M. A., Zhang, M., et al. (2009). Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice. Proc. Natl. Acad. Sci. U S A 106, 20960-20965. doi: 10.1073/pnas.0911405106.
25. Chu, Y., Jin, X., Parada, I., Pesic, A., Stevens, B., Barres, B., et al. (2010). Enhanced synaptic connectivity and epilepsy in C1q knockout mice. Proc. Natl. Acad. Sci. U S A 107, 7975-7980. doi: 10.1073/pnas.0913449107.
26. Cole, D. S., Hughes, T. R., Gasque, P., and Morgan, B. P. (2006). Complement regulator loss on apoptotic neuronal cells causes increased complement activation and promotes both phagocytosis and cell lysis. Mol. Immunol. 43, 1953-1964. doi: 10.1016/j.molimm.2005.11.015.
27. Collard, C. D., Montalto, M. C., Reenstra, W. R., Buras, J. A., and Stahl, G. L. (2001). Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1. Am. J. Pathol. 159, 1045-1054. doi: 10.1016/s0002-9440(10)61779-8.
28. Collard, C. D., Väkevä, A., Morrissey, M. A., Agah, A., Rollins, S. A., Reenstra, W. R., et al. (2000). Complement activation after oxidative stress: role of the lectin complement pathway. Am. J. Pathol. 156, 1549-1556. doi: 10.1016/S0002-9440(10)65026-2.
29. Corbyn, Z. (2014). Stroke: a growing global burden. Nature 510, S2-S3. doi: 10.1038/510S2a.
30. Corriveau, C. C., Madara, P. J., Van Dervort, A. L., Tropea, M. M., Wesley, R. A., and Danner, R. L. (1998). Effects of nitric oxide on chemotaxis and endotoxin-induced interleukin-8 production in human neutrophils. J. Infect. Dis. 177, 116-126. doi: 10.1086/513829.
31. Daborg, J., Andreasson, U., Pekna, M., Lautner, R., Hanse, E., Minthon, L., et al. (2012). Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer's disease. J. Neural Transm. 119, 789-797. doi: 10.1007/s00702-012-0797-8.
32. Datwani, A., McConnell, M. J., Kanold, P. O., Micheva, K. D., Busse, B., Shamloo, M., et al. (2009). Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity. Neuron 64, 463-470. doi: 10.1016/j.neuron.2009.10.015.
33. Davis, A. E., Lu, F., and Mejia, P. (2010). C1 inhibitor, a multi-functional serine protease inhibitor. Thromb. Haemost. 104, 886-893. doi: 10.1160/TH10-01-0073.
34. de la Rosa, X., Cervera, A., Kristoffersen, A. K., Valdés, C. P., Varma, H. M., Justicia, C., et al. (2014). Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice. Stroke 45, 1453-1459. doi: 10.1161/STROKEAHA.113.004111.
35. Depboylu, C., Schäfer, M. K.-H., Arias-Carrión, O., Oertel, W. H., Weihe, E., and Höglinger, G. U. (2011a). Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease. J. Neuropathol. Exp. Neurol. 70, 125-132. doi: 10.1097/NEN.0b013e31820805b9.
36. Depboylu, C., Schorlemmer, K., Klietz, M., Oertel, W. H., Weihe, E., Höglinger, G. U., et al. (2011b). Upregulation of microglial C1q expression has no effects on nigrostriatal dopaminergic injury in the MPTP mouse model of Parkinson disease. J. Neuroimmunol. 236, 39-46. doi: 10.1016/j.jneuroim.2011.05.006.
37. De Simoni, M. G., Rossi, E., Storini, C., Pizzimenti, S., Echart, C., and Bergamaschini, L. (2004). The powerful neuroprotective action of C1-inhibitor on brain ischemia-reperfusion injury does not require C1q. Am. J. Pathol. 164, 1857-1863. doi: 10.1016/s0002-9440(10)63744-3.
38. De Simoni, M. G., Storini, C., Barba, M., Catapano, L., Arabia, A. M., Rossi, E., et al. (2003). Neuroprotection by complement (C1) inhibitor in mouse transient brain ischemia. J. Cereb. Blood Flow Metab. 23, 232-239. doi: 10.1097/00004647-200302000-00010.
39. Dobó, J., Schroeder, V., Jenny, L., Cervenak, L., Závodszky, P., and Gál, P. (2014). Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation. Mol. Immunol. 61, 69-78. doi: 10.1016/j.molimm.2014.05.013.
40. Ducruet, A. F., Hassid, B. G., Mack, W. J., Sosunov, S. A., Otten, M. L., Fusco, D. J., et al. (2008). C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent. J. Cereb. Blood Flow Metab. 28, 1048-1058. doi: 10.1038/sj.jcbfm.9600608.
41. Eggleton, P., Tenner, A. J., and Reid, K. B. (2000). C1q receptors. Clin. Exp. Immunol. 120, 406-412. doi: 10.1046/j.1365-2249.2000.01218.x.
42. Ehrlich, P., and Morgenroth, J. (1899). Zur Theorie der Lysenwirkung [in German]. Berl. Klin. Wschr. 36, 6-9.
43. Ehrnthaller, C., Ignatius, A., Gebhard, F., and Huber-Lang, M. (2011). New insights of an old defense system: structure, function and clinical relevance of the complement system. Mol. Med. 17, 317-329. doi: 10.2119/molmed.2010.00149.
44. Elvington, A., Atkinson, C., Zhu, H., Yu, J., Takahashi, K., Stahl, G. L., et al. (2012). The alternative complement pathway propagates inflammation and injury in murine ischemic stroke. J. Immunol. 189, 4640-4647. doi: 10.4049/jimmunol.1201904.
45. Figueroa, E., Gordon, L. E., Feldhoff, P. W., and Lassiter, H. A. (2005). The administration of cobra venom factor reduces post-ischemic cerebral injury in adult and neonatal rats. Neurosci. Lett. 380, 48-53. doi: 10.1016/j.neulet.2005.01.027.
46. Finehout, E. J., Franck, Z., and Lee, K. H. (2005). Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease. Dis. Markers 21, 93-101. doi: 10.1155/2005/806573.
47. Fiske, B. K., and Brunjes, P. C. (2000). Microglial activation in the developing rat olfactory bulb. Neuroscience 96, 807-815. doi: 10.1016/s0306-4522(99)00601-6.
48. Flierman, R., and Daha, M. R. (2007). The clearance of apoptotic cells by complement. Immunobiology 212, 363-370. doi: 10.1016/j.imbio.2006.11.005.
49. Fluiter, K., Opperhuizen, A. L., Morgan, B. P., Baas, F., and Ramaglia, V. (2014). Inhibition of the membrane attack complex of the complement system reduces secondary neuroaxonal loss and promotes neurologic recovery after traumatic brain injury in mice. J. Immunol. 192, 2339-2348. doi: 10.4049/jimmunol.1302793.
50. 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. J. Immunol. 183, 1375-1383. doi: 10.4049/jimmunol.0901005.
51. Fonseca, M. I., Kawas, C. H., Troncoso, J. C., and Tenner, A. J. (2004a). Neuronal localization of C1q in preclinical Alzheimer's disease. Neurobiol. Dis. 15, 40-46. doi: 10.1016/j.nbd.2003.09.004.
52. Fonseca, M. I., McGuire, S. O., Counts, S. E., and Tenner, A. J. (2013). Complement activation fragment C5a receptors, CD88 and C5L2, are associated with neurofibrillary pathology. J. Neuroinflammation 10:25. doi: 10.1186/1742-2094-10-25.
53. Fonseca, M. I., Zhou, J., Botto, M., and Tenner, A. J. (2004b). Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J. Neurosci. 24, 6457-6465. doi: 10.1523/jneurosci.0901-04.2004.
54. Füst, G., Munthe-Fog, L., Illes, Z., Széplaki, G., Molnar, T., Pusch, G., et al. (2011). Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke. J. Neuroinflammation 8:185. doi: 10.1186/1742-2094-8-185.
55. Gasque, P., Dean, Y. D., McGreal, E. P., VanBeek, J., and Morgan, B. P. (2000). Complement components of the innate immune system in health and disease in the CNS. Immunopharmacology 49, 171-186. doi: 10.1016/s0162-3109(00)80302-1.
56. Gesuete, R., Storini, C., Fantin, A., Stravalaci, M., Zanier, E. R., Orsini, F., et al. (2009). Recombinant C1 inhibitor in brain ischemic injury. Ann. Neurol. 66, 332-342. doi: 10.1002/ana.21740.
57. Goldknopf, I. L., Sheta, E. A., Bryson, J., Folsom, B., Wilson, C., Duty, J., et al. (2006). Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem. Biophys. Res. Commun. 342, 1034-1039. doi: 10.1016/j.bbrc.2006.02.051.
58. Grewal, R. P., Morgan, T. E., and Finch, C. E. (1999). C1qB and clusterin mRNA increase in association with neurodegeneration in sporadic amyotrophic lateral sclerosis. Neurosci. Lett. 271, 65-67. doi: 10.1016/s0304-3940(99)00496-6.
59. Harhausen, D., Khojasteh, U., Stahel, P. F., Morgan, B. P., Nietfeld, W., Dirnagl, U., et al. (2010). Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice. J. Neuroinflammation 7:15. doi: 10.1186/1742-2094-7-15.
60. Heese, K., Hock, C., and Otten, U. (1998). Inflammatory signals induce neurotrophin expression in human microglial cells. J. Neurochem. 70, 699-707. doi: 10.1046/j.1471-4159.1998.70020699.x.
61. Heimann, A., Takeshima, T., Horstick, G., and Kempski, O. (1999). C1-esterase inhibitor reduces infarct volume after cortical vein occlusion. Brain Res. 838, 210-213. doi: 10.1016/s0006-8993(99)01740-0.
62. Heurich, B., El Idrissi, N. B., Donev, R. M., Petri, S., Claus, P., Neal, J., et al. (2011). Complement upregulation and activation on motor neurons and neuromuscular junction in the SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. J. Neuroimmunol. 235, 104-109. doi: 10.1016/j.jneuroim.2011.03.011.
63. Heydenreich, N., Nolte, M. W., Göb, E., Langhauser, F., Hofmeister, M., Kraft, P., et al. (2012). C1-inhibitor protects from brain ischemia-reperfusion injury by combined antiinflammatory and antithrombotic mechanisms. Stroke 43, 2457-2467. doi: 10.1161/STROKEAHA.112.660340.
64. Hill, J. H., and Ward, P. A. (1971). The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J. Exp. Med. 133, 885-900. doi: 10.1084/jem.133.4.885.
65. Hooks, B. M., and Chen, C. (2006). Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse. Neuron 52, 281-291. doi: 10.1016/j.neuron.2006.07.007.
66. Howell, G. R., Macalinao, D. G., Sousa, G. L., Walden, M., Soto, I., Kneeland, S. C., et al. (2011). Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma. J. Clin. Invest. 121, 1429-1444. doi: 10.1172/JCI44646.
67. 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. Nat. Med. 12, 682-687. doi: 10.1038/nm1419.
68. Hugo, J., and Ganguli, M. (2014). Dementia and cognitive impairment: epidemiology, diagnosis and treatment. Clin. Geriatr. Med. 30, 421-442. doi: 10.1016/j.cger.2014.04.001.
69. Huh, G. S., Boulanger, L. M., Du, H., Riquelme, P. A., Brotz, T. M., and Shatz, C. J. (2000). Functional requirement for class I MHC in CNS development and plasticity. Science 290, 2155-2159. doi: 10.1126/science.290.5499.2155.
70. 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. J. Neuroimmunol. 210, 52-62. doi: 10.1016/j.jneuroim.2009.01.028.
71. Hummelshoj, T., Fog, L. M., Madsen, H. O., Sim, R. B., and Garred, P. (2008). Comparative study of the human ficolins reveals unique features of Ficolin-3 (Hakata antigen). Mol. Immunol. 45, 1623-1632. doi: 10.1016/j.molimm.2007.10.006.
72. Jani, P. K., Kajdácsi, E., Megyeri, M., Dobó, J., Doleschall, Z., Futosi, K., et al. (2014). MASP-1 induces a unique cytokine pattern in endothelial cells: a novel link between complement system and neutrophil granulocytes. PLoS One 9:e87104. doi: 10.1371/journal.pone.0087104.
73. Järlestedt, K., Rousset, C. I., Ståhlberg, A., Sourkova, H., Atkins, A. L., Thornton, C., et al. (2013). Receptor for complement peptide C3a: a therapeutic target for neonatal hypoxic-ischemic brain injury. FASEB J. 27, 3797-3804. doi: 10.1096/fj.13-230011.
74. Jiang, H., Burdick, D., Glabe, C. G., Cotman, C. W., and Tenner, A. J. (1994). beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. J. Immunol. 152, 5050-5059.
75. Kaczorowski, S. L., Schiding, J. K., Toth, C. A., and Kochanek, P. M. (1995). Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J. Cereb. Blood Flow Metab. 15, 860-864. doi: 10.1038/jcbfm.1995.107.
76. Kerr, F. K., Thomas, A. R., Wijeyewickrema, L. C., Whisstock, J. C., Boyd, S. E., Kaiserman, D., et al. (2008). Elucidation of the substrate specificity of the MASP-2 protease of the lectin complement pathway and identification of the enzyme as a major physiological target of the serpin, C1-inhibitor. Mol. Immunol. 45, 670-677. doi: 10.1016/j.molimm.2007.07.008.
77. 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. doi: 10.1227/01.NEU.0000335079.70222.8D.
78. Kim, D. D., and Song, W.-C. (2006). Membrane complement regulatory proteins. Clin. Immunol. 118, 127-136. doi: 10.1016/j.clim.2005.10.014.
79. Kishore, U., Ghai, R., Greenhough, T. J., Shrive, A. K., Bonifati, D. M., Gadjeva, M. G., et al. (2004). Structural and functional anatomy of the globular domain of complement protein C1q. Immunol. Lett. 95, 113-128. doi: 10.1016/j.imlet.2004.06.015.
80. Kjaer, T. R., Thiel, S., and Andersen, G. R. (2013). Toward a structure-based comprehension of the lectin pathway of complement. Mol. Immunol. 56, 413-422. doi: 10.1016/j.molimm.2013.05.007.
81. Kossmann, T., Stahel, P. F., Morganti-Kossmann, M. C., Jones, J. L., and Barnum, S. R. (1997). Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. J. Neuroimmunol. 73, 63-69. doi: 10.1016/s0165-5728(96)00164-6.
82. Lanzrein, A. S., Jobst, K. A., Thiel, S., Jensenius, J. C., Sim, R. B., Perry, V. H., et al. (1998). Mannan-binding lectin in human serum, cerebrospinal fluid and brain tissue and its role in Alzheimer's disease. Neuroreport 9, 1491-1495. doi: 10.1097/00001756-199805110-00045.
83. Lassiter, H. A., Feldhoff, R. C., Dabhia, N., Parker, J. C., and Feldhoff, P. W. (2001). Complement inhibition does not reduce post-hypoxic-ischemic cerebral injury in 21-day-old rats. Neurosci. Lett. 302, 37-40. doi: 10.1016/s0304-3940(01)01653-6.
84. Lee, J. D., Kamaruzaman, N. A., Fung, J. N. T., Taylor, S. M., Turner, B. J., Atkin, J. D., et al. (2013). Dysregulation of the complement cascade in the hSOD1G93A transgenic mouse model of amyotrophic lateral sclerosis. J. Neuroinflammation 10:119. doi: 10.1186/1742-2094-10-119.
85. Leinhase, I., Rozanski, M., Harhausen, D., Thurman, J. M., Schmidt, O. I., Hossini, A. M., et al. (2007). 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 4:13. doi: 10.1186/1742-2094-4-13.
86. Leinhase, I., Schmidt, O. I., Thurman, J. M., Hossini, A. M., Rozanski, M., Taha, M. E., et al. (2006). Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression and neurological outcome after traumatic brain injury. Exp. Neurol. 199, 454-464. doi: 10.1016/j.expneurol.2006.01.033.
87. Lew, S. M., Gross, C. E., Bednar, M. M., Russell, S. J., Fuller, S. P., Ellenberger, C. L., et al. (1999). Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke. Brain Res. Bull. 48, 325-331. doi: 10.1016/s0361-9230(99)00004-0.
88. Lindsberg, P. J., Ohman, J., Lehto, T., Karjalainen-Lindsberg, M. L., Paetau, A., Wuorimaa, T., et al. (1996). Complement activation in the central nervous system following blood-brain barrier damage in man. Ann. Neurol. 40, 587-596. doi: 10.1002/ana.410400408.
89. Lingsma, H. F., Roozenbeek, B., Steyerberg, E. W., Murray, G. D., and Maas, A. I. R. (2010). Early prognosis in traumatic brain injury: from prophecies to predictions. Lancet Neurol. 9, 543-554. doi: 10.1016/S1474-4422(10)70065-X.
90. Lister, K. J., James, W. G., and Hickey, M. J. (2007). Immune complexes mediate rapid alterations in microvascular permeability: roles for neutrophils, complement and platelets. Microcirculation 14, 709-722. doi: 10.1080/10739680701404879.
91. Liu, Z. M., Zhu, S. M., Qin, X. J., Cheng, Z. D., Liu, M. Y., Zhang, H. M., et al. (2010). Silencing of C5a receptor gene with siRNA for protection from Gram-negative bacterial lipopolysaccharide-induced vascular permeability. Mol. Immunol. 47, 1325-1333. doi: 10.1016/j.molimm.2009.11.001.
92. Lobsiger, C. S., Boillée, S., and Cleveland, D. W. (2007). Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons. Proc. Natl. Acad. Sci. U S A 104, 7319-7326. doi: 10.1073/pnas.0702230104.
93. Lobsiger, C. S., Boillée, S., Pozniak, C., Khan, A. M., McAlonis-Downes, M., Lewcock, J. W., et al. (2013). C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice. Proc. Natl. Acad. Sci. U S A 110, E4385-E4392. doi: 10.1073/pnas.1318309110.
94. Loeffler, D. A., Camp, D. M., and Bennett, D. A. (2008). Plaque complement activation and cognitive loss in Alzheimer's disease. J. Neuroinflammation 5:9. doi: 10.1186/1742-2094-5-9.
95. Longhi, L., Orsini, F., De Blasio, D., Fumagalli, S., Ortolano, F., Locatelli, M., et al. (2014). Mannose-binding lectin is expressed after clinical and experimental traumatic brain injury and its deletion is protective*. Crit. Care Med. 42, 1910-1918. doi: 10.1097/CCM.0000000000000399.
96. Longhi, L., Perego, C., Ortolano, F., Zanier, E. R., Bianchi, P., Stocchetti, N., et al. (2009). C1-inhibitor attenuates neurobehavioral deficits and reduces contusion volume after controlled cortical impact brain injury in mice. Crit. Care Med. 37, 659-665. doi: 10.1097/CCM.0B013e318195998a.
97. Lozada, C., Levin, R. I., Huie, M., Hirschhorn, R., Naime, D., Whitlow, M., et al. (1995). Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1. Proc. Natl. Acad. Sci. U S A 92, 8378-8382. doi: 10.1073/pnas.92.18.8378.
98. Mack, W. J., Sughrue, M. E., Ducruet, A. F., Mocco, J., Sosunov, S. A., Hassid, B. G., et al. (2006). Temporal pattern of C1q deposition after transient focal cerebral ischemia. J. Neurosci. Res. 83, 883-889. doi: 10.1002/jnr.20775.
99. Maier, M., Peng, Y., Jiang, L., Seabrook, T. J., Carroll, M. C., and Lemere, C. A. (2008). Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J. Neurosci. 28, 6333-6341. doi: 10.1523/JNEUROSCI.0829-08.2008.
100. Markiewski, M. M., Nilsson, B., Ekdahl, K. N., Mollnes, T. E., and Lambris, J. D. (2007). Complement and coagulation: strangers or partners in crime? Trends Immunol. 28, 184-192. doi: 10.1016/j.it.2007.02.006.
101. McGeer, P. L., and McGeer, E. G. (2004). Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat. Disord. 10(Suppl. 1), S3-S7. doi: 10.1016/j.parkreldis.2004.01.005.
102. McMullen, M. E., Hart, M. L., Walsh, M. C., Buras, J., Takahashi, K., and Stahl, G. L. (2006). Mannose-binding lectin binds IgM to activate the lectin complement pathway in vitro and in vivo. Immunobiology 211, 759-766. doi: 10.1016/j.imbio.2006.06.011.
103. Megyeri, M., Makó, V., Beinrohr, L., Doleschall, Z., Prohászka, Z., Cervenak, L., et al. (2009). Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function. J. Immunol. 183, 3409-3416. doi: 10.4049/jimmunol.0900879.
104. Meraz-Ríos, M. A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hernández, J., and Campos-Peña, V. (2013). Inflammatory process in Alzheimer's disease. Front. Integr. Neurosci. 7:59. doi: 10.3389/fnint.2013.00059.
105. Mitchell, D. A., Pickering, M. C., Warren, J., Fossati-Jimack, L., Cortes-Hernandez, J., Cook, H. T., et al. (2002). C1q deficiency and autoimmunity: the effects of genetic background on disease expression. J. Immunol. 168, 2538-2543. doi: 10.4049/jimmunol.168.5.2538.
106. Mocco, J., Mack, W. J., Ducruet, A. F., Sosunov, S. A., Sughrue, M. E., Hassid, B. G., et al. (2006a). Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ. Res. 99, 209-217. doi: 10.1161/01.res.0000232544.90675.42.
107. Mocco, J., Wilson, D. A., Komotar, R. J., Sughrue, M. E., Coates, K., Sacco, R. L., et al. (2006b). Alterations in plasma complement levels after human ischemic stroke. Neurosurgery 59, 28-33; discussion 28-33. doi: 10.1227/01.neu.0000219221.14280.65.
108. Møller-Kristensen, M., Wang, W., Ruseva, M., Thiel, S., Nielsen, S., Takahashi, K., et al. (2005). Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury. Scand. J. Immunol. 61, 426-434. doi: 10.1111/j.1365-3083.2005.01591.x.
109. Monsinjon, T., Gasque, P., Chan, P., Ischenko, A., Brady, J. J., and Fontaine, M. C. (2003). Regulation by complement C3a and C5a anaphylatoxins of cytokine production in human umbilical vein endothelial cells. FASEB J. 17, 1003-1014. doi: 10.1096/fj.02-0737com.
110. More, S. V., Kumar, H., Kim, I. S., Song, S.-Y., and Choi, D.-K. (2013). Cellular and molecular mediators of neuroinflammation in the pathogenesis of Parkinson's disease. Mediators Inflamm. 2013:952375. doi: 10.1155/2013/952375.
111. Morgan, B. P. (1990). Complement: Clinical Aspects and Relevance to Disease. UK: Academic Press.
112. Morgan, B. P., and Gasque, P. (1997). Extrahepatic complement biosynthesis: where, when and why? Clin. Exp. Immunol. 107, 1-7. doi: 10.1046/j.1365-2249.1997.d01-890.x.
113. Neher, J. J., Neniskyte, U., and Brown, G. C. (2012). Primary phagocytosis of neurons by inflamed microglia: potential roles in neurodegeneration. Front. Pharmacol. 3:27. doi: 10.3389/fphar.2012.00027.
114. Neher, J. J., Neniskyte, U., Zhao, J.-W., Bal-Price, A., Tolkovsky, A. M., and Brown, G. C. (2011). Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J. Immunol. 186, 4973-4983. doi: 10.4049/jimmunol.1003600.
115. Nesargikar, P. N., Spiller, B., and Chavez, R. (2012). The complement system: history, pathways, cascade and inhibitors. Eur. J. Microbiol. Immunol. (Bp) 2, 103-111. doi: 10.1556/EuJMI.2.2012.2.2.
116. 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. J. Immunol. 166, 4154-4162. doi: 10.4049/jimmunol.166.6.4154.
117. Oroszlán, M., Daha, M. R., Cervenak, L., Prohászka, Z., Füst, G., and Roos, A. (2007). MBL and C1q compete for interaction with human endothelial cells. Mol. Immunol. 44, 1150-1158. doi: 10.1016/j.molimm.2006.06.015.
118. Orsini, F., Villa, P., Parrella, S., Zangari, R., Zanier, E. R., Gesuete, R., et al. (2012). Targeting mannose-binding lectin confers long-lasting protection with a surprisingly wide therapeutic window in cerebral ischemia. Circulation 126, 1484-1494. doi: 10.1161/CIRCULATIONAHA.112.103051.
119. Osthoff, M., Katan, M., Fluri, F., Schuetz, P., Bingisser, R., Kappos, L., et al. (2011). Mannose-binding lectin deficiency is associated with smaller infarction size and favorable outcome in ischemic stroke patients. PLoS One 6:e21338. doi: 10.1371/journal.pone.0021338.
120. Patterson, P. H. (2011). Maternal infection and immune involvement in autism. Trends Mol. Med. 17, 389-394. doi: 10.1016/j.molmed.2011.03.001.
121. Pavlov, V. I., Skjoedt, M.-O., Siow Tan, Y., Rosbjerg, A., Garred, P., and Stahl, G. L. (2012). Endogenous and natural complement inhibitor attenuates myocardial injury and arterial thrombogenesis. Circulation 126, 2227-2235. doi: 10.1161/CIRCULATIONAHA.112.123968.
122. Pavlovski, D., Thundyil, J., Monk, P. N., Wetsel, R. A., Taylor, S. M., and Woodruff, T. M. (2012). Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis. FASEB J. 26, 3680-3690. doi: 10.1096/fj.11-202382.
123. Pedersen, E. D., Løberg, E. M., Vege, E., Daha, M. R., Maehlen, J., and Mollnes, T. E. (2009). In situ deposition of complement in human acute brain ischaemia. Scand. J. Immunol. 69, 555-562. doi: 10.1111/j.1365-3083.2009.02253.x.
124. Pedersen, E. D., Waje-Andreassen, U., Vedeler, C. A., Aamodt, G., and Mollnes, T. E. (2004). Systemic complement activation following human acute ischaemic stroke. Clin. Exp. Immunol. 137, 117-122. doi: 10.1111/j.1365-2249.2004.02489.x.
125. Pisalyaput, K., and Tenner, A. J. (2008). Complement component C1q inhibits beta-amyloid-and serum amyloid P-induced neurotoxicity via caspase-and calpain-independent mechanisms. J. Neurochem. 104, 696-707. doi: 10.1111/j.1471-4159.2007.05012.x.
126. 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 J. 25, 1364-1374. doi: 10.1038/sj.emboj.7601004.
127. Rancan, M., Morganti-Kossmann, M. C., Barnum, S. R., Saft, S., Schmidt, O. I., Ertel, W., et al. (2003). Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice. J. Cereb. Blood Flow Metab. 23, 1070-1074. doi: 10.1097/01.wcb.0000084250.20114.2c.
128. Reichwald, J., Danner, S., Wiederhold, K.-H., and Staufenbiel, M. (2009). Expression of complement system components during aging and amyloid deposition in APP transgenic mice. J. Neuroinflammation 6:35. doi: 10.1186/1742-2094-6-35.
129. Ricklin, D., Hajishengallis, G., Yang, K., and Lambris, J. D. (2010). Complement: a key system for immune surveillance and homeostasis. Nat. Immunol. 11, 785-797. doi: 10.1038/ni.1923.
130. Ricklin, D., and Lambris, J. D. (2007). Complement-targeted therapeutics. Nat. Biotechnol. 25, 1265-1275. doi: 10.1038/nbt1342.
131. Rogers, J., Cooper, N. R., Webster, S., Schultz, J., McGeer, P. L., Styren, S. D., et al. (1992). Complement activation by beta-amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. U S A 89, 10016-10020. doi: 10.1073/pnas.89.21.10016.
132. Rutkowski, M. J., Sughrue, M. E., Kane, A. J., Ahn, B. J., Fang, S., and Parsa, A. T. (2010). The complement cascade as a mediator of tissue growth and regeneration. Inflamm. Res. 59, 897-905. doi: 10.1007/s00011-010-0220-6.
133. Savill, J., Dransfield, I., Gregory, C., and Haslett, C. (2002). A blast from the past: clearance of apoptotic cells regulates immune responses. Nat. Rev. Immunol. 2, 965-975. doi: 10.1038/nri957.
134. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., et al. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705. doi: 10.1016/j.neuron.2012.03.026.
135. Schäfer, M. K., Schwaeble, W. J., Post, C., Salvati, P., Calabresi, M., Sim, R. B., et al. (2000). Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia. J. Immunol. 164, 5446-5452. doi: 10.4049/jimmunol.164.10.5446.
136. Schraufstatter, I. U., Trieu, K., Sikora, L., Sriramarao, P., and DiScipio, R. (2002). Complement c3a and c5a induce different signal transduction cascades in endothelial cells. J. Immunol. 169, 2102-2110. doi: 10.4049/jimmunol.169.4.2102.
137. 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. J. Neuroimmunol. 155, 55-63. doi: 10.1016/j.jneuroim.2004.06.003.
138. Shen, Y., Lue, L., Yang, L., Roher, A., Kuo, Y., Strohmeyer, R., et al. (2001). Complement activation by neurofibrillary tangles in Alzheimer's disease. Neurosci. Lett. 305, 165-168. doi: 10.1016/s0304-3940(01)01842-0.
139. Shinjyo, N., Ståhlberg, A., Dragunow, M., Pekny, M., and Pekna, M. (2009). Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells. Stem Cells 27, 2824-2832. doi: 10.1002/stem.225.
140. Singhrao, S. K., Neal, J. W., Rushmere, N. K., Morgan, B. P., and Gasque, P. (2000). Spontaneous classical pathway activation and deficiency of membrane regulators render human neurons susceptible to complement lysis. Am. J. Pathol. 157, 905-918. doi: 10.1016/s0002-9440(10)64604-4.
141. Sjölander, A., Minthon, L., Nuytinck, L., Vanmechelen, E., Blennow, K., and Nilsson, S. (2013). Functional mannose-binding lectin haplotype variants are associated with Alzheimer's disease. J. Alzheimers Dis. 35, 121-127. doi: 10.3233/JAD-122044.
142. Sta, M., Sylva-Steenland, R. M. R., Casula, M., de Jong, J. M. B. V., Troost, D., Aronica, E., et al. (2011). Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation. Neurobiol. Dis. 42, 211-220. doi: 10.1016/j.nbd.2011.01.002.
143. Stahel, P. F., Flierl, M. A., Morgan, B. P., Persigehl, I., Stoll, C., Conrad, C., et al. (2009). Absence of the complement regulatory molecule CD59a leads to exacerbated neuropathology after traumatic brain injury in mice. J. Neuroinflammation 6:2. doi: 10.1186/1742-2094-6-2.
144. Stahel, P. F., Morganti-Kossmann, M. C., Perez, D., Redaelli, C., Gloor, B., Trentz, O., et al. (2001). 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 18, 773-781. doi: 10.1089/089771501316919139.
145. Stephan, A. H., Barres, B. A., and Stevens, B. (2012). The complement system: an unexpected role in synaptic pruning during development and disease. Annu. Rev. Neurosci. 35, 369-389. doi: 10.1146/annurev-neuro-061010-113810.
146. Stephan, A. H., Madison, D. V., Mateos, J. M., Fraser, D. A., Lovelett, E. A., Coutellier, L., et al. (2013). A dramatic increase of C1q protein in the CNS during normal aging. J. Neurosci. 33, 13460-13474. doi: 10.1523/JNEUROSCI.1333-13.2013.
147. 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. doi: 10.1016/j.cell.2007.10.036.
148. Stokowska, A., Olsson, S., Holmegaard, L., Jood, K., Blomstrand, C., Jern, C., et al. (2013). Cardioembolic and small vessel disease stroke show differences in associations between systemic C3 levels and outcome. PLoS One 8:e72133. doi: 10.1371/journal.pone.0072133.
149. Stoltzner, S. E., Grenfell, T. J., Mori, C., Wisniewski, K. E., Wisniewski, T. M., Selkoe, D. J., et al. (2000). Temporal accrual of complement proteins in amyloid plaques in down's syndrome with Alzheimer's disease. Am. J. Pathol. 156, 489-499. doi: 10.1016/S0002-9440(10)64753-0.
150. Storini, C., Rossi, E., Marrella, V., Distaso, M., Veerhuis, R., Vergani, C., et al. (2005). C1-inhibitor protects against brain ischemia-reperfusion injury via inhibition of cell recruitment and inflammation. Neurobiol. Dis. 19, 10-17. doi: 10.1016/j.nbd.2004.11.001.
151. Széplaki, G., Szegedi, R., Hirschberg, K., Gombos, T., Varga, L., Karádi, I., et al. (2009). Strong complement activation after acute ischemic stroke is associated with unfavorable outcomes. Atherosclerosis 204, 315-320. doi: 10.1016/j.atherosclerosis.2008.07.044.
152. Takeuchi, S., Fujiwara, N., Ido, A., Oono, M., Takeuchi, Y., Tateno, M., et al. (2010). Induction of protective immunity by vaccination with wild-type apo superoxide dismutase 1 in mutant SOD1 transgenic mice. J. Neuropathol. Exp. Neurol. 69, 1044-1056. doi: 10.1097/NEN.0B013e3181f4a90a.
153. Tedesco, F., Pausa, M., Nardon, E., Introna, M., Mantovani, A., and Dobrina, A. (1997). The cytolytically inactive terminal complement complex activates endothelial cells to express adhesion molecules and tissue factor procoagulant activity. J. Exp. Med. 185, 1619-1627. doi: 10.1084/jem.185.9.1619.
154. Ten, V. S., Sosunov, S. A., Mazer, S. P., Stark, R. I., Caspersen, C., Sughrue, M. E., et al. (2005). C1q-deficiency is neuroprotective against hypoxic-ischemic brain injury in neonatal mice. Stroke 36, 2244-2250. doi: 10.1161/01.str.0000182237.20807.d0.
155. Tsuboi, Y., and Yamada, T. (1994). Increased concentration of C4d complement protein in CSF in amyotrophic lateral sclerosis. J. Neurol. Neurosurg. Psychiatry 57, 859-861. doi: 10.1136/jnnp.57.7.859.
156. 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. Exp. Neurol. 161, 373-382. doi: 10.1006/exnr.1999.7273.
157. van den Berg, R. H., Faber-Krol, M. C., Sim, R. B., and Daha, M. R. (1998). The first subcomponent of complement, C1q, triggers the production of IL-8, IL-6 and monocyte chemoattractant peptide-1 by human umbilical vein endothelial cells. J. Immunol. 161, 6924-6930.
158. Vasthare, U. S., Barone, F. C., Sarau, H. M., Rosenwasser, R. H., DiMartino, M., Young, W. F., et al. (1998). Complement depletion improves neurological function in cerebral ischemia. Brain Res. Bull. 45, 413-419. doi: 10.1016/s0361-9230(97)00408-5.
159. Veerhuis, R., Nielsen, H. M., and Tenner, A. J. (2011). Complement in the brain. Mol. Immunol. 48, 1592-1603. doi: 10.1016/j.molimm.2011.04.003.
160. Veerhuis, R., Van Breemen, M. J., Hoozemans, J. M., Morbin, M., Ouladhadj, J., Tagliavini, F., et al. (2003). Amyloid beta plaque-associated proteins C1q and SAP enhance the Abeta1-42 peptide-induced cytokine secretion by adult human microglia in vitro. Acta Neuropathol. 105, 135-144. doi: 10.1007/s00401-002-0624-7.
161. Wagner, E., and Frank, M. M. (2010). Therapeutic potential of complement modulation. Nat. Rev. Drug Discov. 9, 43-56. doi: 10.1038/nrd3011.
162. Wang, Y., Hancock, A. M., Bradner, J., Chung, K. A., Quinn, J. F., Peskind, E. R., et al. (2011). Complement 3 and factor h in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease and multiple-system atrophy. Am. J. Pathol. 178, 1509-1516. doi: 10.1016/j.ajpath.2011.01.006.
163. Wang, Y., Li, Y., Dalle Lucca, S. L., Simovic, M., Tsokos, G. C., and Dalle Lucca, J. J. (2010). Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury. J. Neuroinflammation 7:24. doi: 10.1186/1742-2094-7-24.
164. Webster, S. D., Galvan, M. D., Ferran, E., Garzon-Rodriguez, W., Glabe, C. G., and Tenner, A. J. (2001). Antibody-mediated phagocytosis of the amyloid beta-peptide in microglia is differentially modulated by C1q. J. Immunol. 166, 7496-7503. doi: 10.4049/jimmunol.166.12.7496.
165. Woodruff, T. M., Ager, R. R., Tenner, A. J., Noakes, P. G., and Taylor, S. M. (2010). The role of the complement system and the activation fragment C5a in the central nervous system. Neuromolecular Med. 12, 179-192. doi: 10.1007/s12017-009-8085-y.
166. Woodruff, T. M., Costantini, K. J., Crane, J. W., Atkin, J. D., Monk, P. N., Taylor, S. M., et al. (2008). The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J. Immunol. 181, 8727-8734. doi: 10.4049/jimmunol.181.12.8727.
167. Wyss-Coray, T., Yan, F., Lin, A. H.-T., Lambris, J. D., Alexander, J. J., Quigg, R. J., et al. (2002). Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice. Proc. Natl. Acad. Sci. U S A 99, 10837-10842. doi: 10.1073/pnas.162350199.
168. Yager, P. H., You, Z., Qin, T., Kim, H.-H., Takahashi, K., Ezekowitz, A. B., et al. (2008). Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. J. Cereb. Blood Flow Metab. 28, 1030-1039. doi: 10.1038/sj.jcbfm.9600605.
169. Yao, J., Harvath, L., Gilbert, D. L., and Colton, C. A. (1990). Chemotaxis by a CNS macrophage, the microglia. J. Neurosci. Res. 27, 36-42. doi: 10.1002/jnr.490270106.
170. Yasojima, K., Schwab, C., McGeer, E. G., and McGeer, P. L. (1999). Up-regulated production and activation of the complement system in Alzheimer's disease brain. Am. J. Pathol. 154, 927-936. doi: 10.1016/s0002-9440(10)65340-0.
171. Yin, W., Ghebrehiwet, B., Weksler, B., and Peerschke, E. I. (2007). Classical pathway complement activation on human endothelial cells. Mol. Immunol. 44, 2228-2234. doi: 10.1016/j.molimm.2006.11.012.
172. You, Z., Yang, J., Takahashi, K., Yager, P. H., Kim, H.-H., Qin, T., et al. (2007). Reduced tissue damage and improved recovery of motor function after traumatic brain injury in mice deficient in complement component C4. J. Cereb. Blood Flow Metab. 27, 1954-1964. doi: 10.1038/sj.jcbfm.9600497.
173. Zanier, E. R., Zangari, R., Munthe-Fog, L., Hein, E., Zoerle, T., Conte, V., et al. (2014). Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage. Neurology 82, 126-134. doi: 10.1212/WNL.0000000000000020.
174. Zanjani, H., Finch, C. E., Kemper, C., Atkinson, J., McKeel, D., Morris, J. C., et al. (2005). Complement activation in very early Alzheimer disease. Alzheimer Dis. Assoc. Disord. 19, 55-66. doi: 10.1097/01.wad.0000165506.60370.94.
175. Zhou, J., Fonseca, M. I., Pisalyaput, K., and Tenner, A. J. (2008). Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease. J. Neurochem. 106, 2080-2092. doi: 10.1111/j.1471-4159.2008.05558.x.
176. Ziccardi, R. J. (1981). Activation of the early components of the classical complement pathway under physiologic conditions. J. Immunol. 126, 1769-1773.