title: Cutting edge: the membrane attack complex of complement is required for the development of murine experimental cerebral malaria.
abstract: Cerebral malaria is the most severe complication of Plasmodium falciparum infection and accounts for a large number of malaria fatalities worldwide. Recent studies demonstrated that C5(-/-) mice are resistant to experimental cerebral malaria (ECM) and suggested that protection was due to loss of C5a-induced inflammation. Surprisingly, we observed that C5aR(-/-) mice were fully susceptible to disease, indicating that C5a is not required for ECM. C3aR(-/-) and C3aR(-/-) × C5aR(-/-) mice were equally susceptible to ECM as were wild-type mice, indicating that neither complement anaphylatoxin receptor is critical for ECM development. In contrast, C9 deposition in the brains of mice with ECM suggested an important role for the terminal complement pathway. Treatment with anti-C9 Ab significantly increased survival time and reduced mortality in ECM. Our data indicate that protection from ECM in C5(-/-) mice is mediated through inhibition of membrane attack complex formation and not through C5a-induced inflammation.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Theresa N
authors.initials: TN
authors.lastname: Ramos
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Darley
authors.forename: Xianzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Oliver
authors.initials: O
authors.lastname: Billker
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.forename: Malika
authors.initials: M
authors.lastname: Ahras
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Wohler
authors.forename: Scott R
authors.initials: SR
authors.lastname: Barnum
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology; D015936:Complement C5a / Q000502:physiology; D003186:Complement C9 / Q000037:antagonists & inhibitors; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors / Q000502:physiology*; D004198:Disease Susceptibility; D007249:Inflammation; D016779:Malaria, Cerebral / Q000209:etiology* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015996:Survival Rate
chemical_list: D003186:Complement C9; D015938:Complement Membrane Attack Complex; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a