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Title: RECOMBINANT BOVINE SOLUBLE CD14 REDUCES FATALITY OF ENDOTOXIN CHALLENGED MICE

Author
item LEE, J - MCGILL U CANADA
item ZHAO, X - MCGILL U CANADA
item Paape, Max

Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: 4/14/2002
Publication Date: 4/27/2004
Citation: Lee, J.W., Zhao, X., Paape, M.J. 2002. Recombinant bovine soluble CD 14 reduces fatality of endotoxin challenged mice [abstract]. BARC Poster Day.

Interpretive Summary:

Technical Abstract: Endotoxin, or lipopolysaccharide (LPS), has been demonstrated to be responsible for the pathogenesis of Gram-negative bacterial infections, such as bovine coliform mastitis. In the US, 300,000 dairy cows are removed from herds or die annually because of acute coliform mastitis. Standard therapy for treating acute coliform mastitis, including administration of potent antibiotics, aggressive fluid resuscitation, and metabolic support, has not been successful in reducing mortality. The cellular response to LPS is modulated by the interaction among LPS, LPS-binding protein and CD14. The production of inflammatory cytokines, including TNF-a, by LPS-activated monocytes/macrophages leads to an overwhelming systemic response and causes death in severe cases. Accumulated evidence shows that the soluble form of CD14 (sCD14) competes with membrane-bound CD14 for LPS and inhibits cell activation. To investigate the protective effect of sCD14, recombinant bovine sCD14 (rbosCD14) was produced by transfected insect sf/9 cells and its biological function was evaluated in mice. Eighty-one 8-wk old BALB/cj female mice were randomly assigned to two groups, and injected intraperitoneally with either LPS (8 mg/gBW, n = 41) or LPS plus rbosCD14 (6.8 mg/gBW, n = 40). Survival rate for LPS and LPS plus rbosCD14 injected mice at 24 h was 30 and 72%. At 48 h survival rates were 7 and 37%. Results indicated that rbosCD14 was able to decrease the fatality of LPS challenged mice. These results suggest use of rbosCD14 as a therapeutic agent for neutralizing LPS during acute endotoxin shock in ruminants. Use of rbosCD14 in the treatment of acute coliform mastitis has the potential of saving US dairymen 1.4 billion dollars annually.