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 the infected central nervous system has not been determined. In this study, we analyzed protein and mRNA expression of two alternative pathway complement activation proteins, C3 and factor B, in the brains of mice with Listeria monocytogenes meningitis. Complement protein levels were found elevated in the cerebrospinal fluid of infected mice, compared with mock-infected animals. In the course of the disease, enhanced C3 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 infiltrating the subarachnoid space, within 12 to 24 hours, expressed mRNA for C3 and factor B. The cellular infiltration increased dramatically up to 72 hours. Intraperitoneal injection of tumor necrosis factor (TNF)-alpha up-regulated C3 and factor B mRNA expression on neurons in normal mice, suggesting that TNF-alpha may represent one cytokine regulating complement expression in this model of bacterial meningitis. However, additional mediators may be involved in regulation of intrathecal complement expression, as infected mice deficient of TNF/lymphotoxin-alpha genes did not demonstrate attenuated complement expression in the brain.
Stahel
P F
PF
Department of Microbiology, University of Alabama at Birmingham 35294, USA.
Frei
K
K
Fontana
A
A
Eugster
H P
HP
Ault
B H
BH
Barnum
S R
SR
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D003176:Complement C3 / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000235:genetics; D011415:Complement Factor B / Q000096:biosynthesis* / Q000134:cerebrospinal fluid / Q000235:genetics; D003170:Complement Pathway, Alternative; D005260:Female; D005786:Gene Expression Regulation; D007962:Leukocytes / Q000378:metabolism; D008089:Listeria monocytogenes; D008088:Listeriosis; D016920:Meningitis, Bacterial / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology
D003176:Complement C3; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011415:Complement Factor B