| The complement system plays an important role in many inflammatory disorders of the CNS, including multiple sclerosis (MS), Alzheimer's disease (AD), bacterial meningitis, and stroke. Virtually all cells of the CNS synthesize a complete repertoire of complement activation components, regulatory proteins, and receptors. Complement activation fragments have been found deposited in lesions of patients with MS, and complement inhibition has been shown to attenuate experimental allergic encephalomyelitis (EAE), which is the mouse model of MS. Previous studies from our laboratory have suggested that the activation fragment C5a plays an important role in EAE, because its receptor (C5aR) was upregulated in expression during all active stages of disease. Taking these results into consideration, I hypothesized that complement component C5 is a key mediator of chronic CNS inflammation during EAE. To test the role of C5a in EAE, I induced disease in C5aR-deficient (C5aR-/- ) and WT mice. To test the reverse proof-of-principle hypothesis, I characterized and induced EAE in mice that express C5a exclusively in the CNS using the astrocyte-specific promoter, glial fibrillary acidic protein (GFAP; C5a/GFAP mice). In both cases I found no significant differences in EAE between the genetically modified and WT mice. To examine the role of C5 as a whole during EAE, I induced disease in two different strains of naturally C5-deficient (C5-/-) mice. There were no significant differences in the clinical course of EAE between either of the strains of C5-/- mice and C5-sufficient mice. Together, these studies indicate that, although C5 may be involved in neuroinflammation during EAE, C5 does not play a crucial role in EAE pathogenesis. |
