EVIDENCE FOR INTRATHECAL SYNTHESIS OF ALTERNATIVE PATHWAY COMPLEMENT ACTIVATION PROTEINS IN EXPERIMENTAL MENINGITIS

Complement has been shown to contribute to intrathecal inflammation in bacterial meningitis, However, the cellular source of complement in t he infected central nervous system has not been determined, In this st udy, we analyzed protein and mRNA expression of two alternative pathwa y complement activation proteins, C3 and factor B, in the brains of mi ce with Listeria monocytogenes meningitis. Complement protein levels w ere found elevated in the cerebrospinal fluid of infected mice, compar ed with mock-infected animals, In the course of the disease, enhanced CS and factor B mRNA expression was detected on pyramidal neurons and Purkinje cells within 6 hours, peaking at 12 hours and then gradually decreasing by 72 hours after infection, In addition, leukocytes infilt rating the subarachnoid space, within 12 to 24 hours, expressed mRNA f or C3 and factor B, The cellular infiltration increased dramatically u p to 72 hours, Intraperitoneal injection of tumor necrosis factor (TNF )-alpha up-regulated C3 and factor B mRNA expression on neurons in nor mal mice, suggesting that TNF-alpha may represent one cytokine regulat ing complement expression in this model of bacterial meningitis, Howev er, additional mediators may be involved in regulation of intrathecal complement expression, as infected mice deficient of TNF/lympkotoxin-a lpha genes bid not demonstrate attenuated complement expression in the brain.