Ornithodoros moubata complement inhibitor (OmCI)—A novel and efficient C5 inhibitor in the pig
Barratt-Due, Andreas; Thorgersen, Ebbe B.; Lindstad, Julie; Pharo, Anne; Nunn, Miles A.; Mollnes, Tom E.. 2010 Ornithodoros moubata complement inhibitor (OmCI)—A novel and efficient C5 inhibitor in the pig. Molecular Immunology, 47. 2205. 10.1016/j.molimm.2010.05.033Full text not available from this repository.
Complement and CD14/TLR4 are two important upstream components of innate immunity. Inflammation induced by these danger sensors may be excessive and detrimental in conditions such as sepsis. Inhibition of complement or CD14/TLR4 differentially attenuate experimentally induced inflammation. Combined inhibition has a more pronounced effect, almost abolishing Escherichia coli (E. coli)-induced cytokine release, oxidative burst and expression of the cell-surface marker CD11b in vitro in human studies. We recently showed that an anti-CD14 antibody attenuated proinflammatory cytokines, granulocyte activation and hypercoagulation in E. coli-induced sepsis in vivo in pigs. Combination with a complement inhibitor might enhance the antiinflammatory effect. The aim of the present study was to explore the efficacy in pig of the Ornithodoros moubata complement inhibitor (OmCI) that specifically binds C5 and prevents release of C5a and formation of the terminal complement complex (TCC). Porcine serum and whole blood anticoagulated with lepuridin was incubated with increasing doses of OmCI and activated with E. coli. A pilot study was additionally conducted in vivo in pigs, whereby sepsis was induced by E. coli and the effect of OmCI on the inflammatory response was investigated. Inhibition of complement activity, as evaluated by functional assay of the three initial pathways, was complete at a dose of 2.5 μg OmCI/mL in vitro and 1 mg OmCI/kg in vivo. TCC formation induced by E. coli was abolished in vitro at 5 μg OmCI/mL whole blood, while expression of wCD11R3, the pig analog of human CD11b, was reduced by more than 50% at 5 μg OmCI/mL whole blood. In vivo, OmCI attenuated the increase in IL-8 and TNF-α, and partly protected against the fall in leukocytes seen in the sepsis control group. In conclusion, OmCI efficiently inhibited pig complement activation, showed additional anti-inflammatory effects and is a promising candidate inhibitor for further sepsis studies in vivo.
|Item Type:||Publication - Article|
|Digital Object Identifier (DOI):||10.1016/j.molimm.2010.05.033|
|Programmes:||CEH Topics & Objectives 2009 - 2012 > Biodiversity > BD Topic 1 - Observations, Patterns, and Predictions for Biodiversity|
|Additional Information. Not used in RCUK Gateway to Research.:||The Abstract is the full text of the article - to access, click on the OFFICIAL URL link|
|NORA Subject Terms:||Biology and Microbiology|
|Date made live:||28 Sep 2010 15:27|
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