{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:26:43Z","timestamp":1790803603026,"version":"4.1.0"},"reference-count":43,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"<jats:p>Although complement activation is known to occur in the setting of severe hemorrhagic shock and tissue trauma (HS\/T), the extent to which complement drives the initial inflammatory response and end-organ damage is uncertain. In this study, complement factor 3-deficient (C3<jats:sup>\u2212\/\u2212<\/jats:sup>) mice and wild-type control mice were subjected to 1.5-h hemorrhagic shock, bilateral femur fracture, and soft tissue injury, followed by 4.5-h resuscitation (HS\/T). C57BL\/6 mice were also given 15 U of cobra venom factor (CVF) or phosphate-buffered saline injected intraperitoneally, followed by HS\/T 24 h later. The results showed that HS\/T resulted in C3 consumption in wild-type mice and C3 deposition in injured livers. C3<jats:sup>\u2212\/\u2212<\/jats:sup>mice had significantly lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and circulating DNA levels, together with much lower circulating interleukin (IL)-6, IL-10, and high-mobility group box 1 (HMGB1) levels. Temporary C3 depletion by CVF preconditioning also led to reduced transaminases and a blunted cytokine release. C3<jats:sup>\u2212\/\u2212<\/jats:sup>mice displayed well-preserved hepatic structure. C3<jats:sup>\u2212\/\u2212<\/jats:sup>mice subjected to HS\/T had higher levels of heme oxygenase-1, which has been associated with tissue protection in HS models. Our data indicate that complement activation contributes to inflammatory pathways and liver damage in HS\/T. This suggests that targeting complement activation in the setting of severe injury could be useful.<\/jats:p>","DOI":"10.1152\/ajpregu.00282.2010","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T03:15:21Z","timestamp":1281582921000},"page":"R1175-R1182","source":"Crossref","is-referenced-by-count":31,"title":["Complement factor 3 deficiency attenuates hemorrhagic shock-related hepatic injury and systemic inflammatory response syndrome"],"prefix":"10.1152","volume":"299","author":[{"given":"Changchun","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and"},{"name":"Department of Hepatobiliary Surgery, Qingdao University Medical School Hospital, Qingdao, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roop","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh Medical 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