{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:59:22Z","timestamp":1791223162952,"version":"4.1.0"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,2,1]]},"abstract":"<jats:p>We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, &amp;lt; 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg\/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P &amp;lt; 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P &amp;lt; 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P &amp;lt; 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P &amp;lt; 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock.<\/jats:p>","DOI":"10.1084\/jem.179.2.569","type":"journal-article","created":{"date-parts":[[2004,6,24]],"date-time":"2004-06-24T07:56:10Z","timestamp":1088063770000},"page":"569-578","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure."],"prefix":"10.1084","volume":"179","author":[{"given":"Z M","family":"Quezado","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W D","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J A","family":"Winkelstein","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Yatsiv","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C A","family":"Koev","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L C","family":"Cork","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R J","family":"Elin","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P Q","family":"Eichacker","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Natanson","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1994,2,1]]},"container-title":["The Journal of experimental medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/2\/569\/1675830\/569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/179\/2\/569\/1675830\/569.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T06:05:11Z","timestamp":1690265111000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/179\/2\/569\/57561\/The-third-component-of-complement-protects-against"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,2,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1994,2,1]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.179.2.569","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,2,1]]}}}