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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.
AuthorsTheresa N Ramos, Meghan M Darley, Xianzhen Hu, Oliver Billker, Julian C Rayner, Malika Ahras, Jillian E Wohler, Scott R Barnum
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 12 Pg. 6657-60 (Jun 15 2011) ISSN: 1550-6606 [Electronic] United States
PMID21572031 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Complement C9
  • Complement Membrane Attack Complex
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Complement C5a
Topics
  • Animals
  • Brain (immunology)
  • Complement C5a (physiology)
  • Complement C9 (antagonists & inhibitors)
  • Complement Membrane Attack Complex (antagonists & inhibitors, physiology)
  • Disease Susceptibility
  • Inflammation
  • Malaria, Cerebral (etiology, immunology)
  • Mice
  • Mice, Knockout
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Survival Rate

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