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Differential Role of Complement in Microvascular Thrombosis in Two Models of Experimental Sepsis
Author(s) -
Stark Ryan,
Rumbaut Rolando
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.681.13
Subject(s) - thrombosis , complement system , sepsis , medicine , immunology , perforation , lipopolysaccharide , antibody , metallurgy , punching , materials science
Bacterial infections can promote a pro‐inflammatory cascade via activation of the complement system; complement activation is associated with a pro‐thrombotic state. We showed previously that microvascular thrombosis is enhanced by two models of experimental sepsis, cecal ligation and perforation (CLP) and endotoxemia (induced by lipopolysaccharide, LPS). Thus, we tested the hypothesis that two key components of the complement system: factor C3 and the receptor for C5a (C5aR), mediate enhanced thrombosis in sepsis. We challenged C3‐ and C5aR‐deficient mice, or wild type control mice, with LPS or CLP. We then assessed the kinetics of photochemical injury‐induced thrombosis in mouse cremaster venules. While LPS promoted microvascular thrombosis in wild type mice as compared to saline controls, it had no effect on thrombosis in mice deficient in either C3 or C5aR (time to thrombotic occlusion was reduced by 37% in wildtype vs 9% in knockouts, p<0.05). In contrast, CLP enhanced thrombosis in both complement‐deficient strains as compared to sham‐operated controls. Our studies to date suggest differential roles of complement in microvascular thrombosis in endotoxemia and polymicrobial sepsis. The mechanisms accounting for this differential response remain to be clarified. Support: T32 HL007939‐07, and a Merit Review Grant from The Department of Veterans Affairs.