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Differential role of Complement 5a Receptor in microvascular thrombosis in two models of experimental sepsis.
Author(s) -
Stark Ryan,
Rumbaut Rolando
Publication year - 2013
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.27.1_supplement.686.2
Subject(s) - sepsis , thrombosis , medicine , immunology , inflammation , lipopolysaccharide , perforation , cytokine , septic shock , punching , materials science , metallurgy
Complement 5a plays a key role in the response to bacterial infections and has been implicated in inflammatory and thrombotic responses in sepsis. We reported previously that microvascular thrombosis is enhanced by two models of experimental sepsis: polymicrobial sepsis induced by cecal ligation and perforation (CLP) and endotoxemia, induced by lipopolysaccharide (LPS). Thus, we hypothesized that the receptor for C5a (C5aR) mediates enhanced thrombosis in experimental sepsis. We challenged C5aR‐deficient mice with LPS (or saline control) or CLP (or sham surgery control) and measured the kinetics of photochemical injury‐induced thrombosis and plasma levels of pro‐inflammatory cytokines IL‐1β, TNF‐α and IL‐6. While LPS had no effect on kinetics of thrombosis in C5aR‐deficient mice, CLP promoted microvascular thrombosis in these mice. Despite the lack of prothrombotic response to LPS, C5aR‐deficient mice had a pronounced systemic pro‐inflammatory cytokine response to LPS. This study provides evidence of a differential role of C5aR on microvascular thrombosis and systemic inflammation in experimental sepsis. Support: T32 HL007939–07, and a Merit Review Grant from The Department of Veterans Affairs.