RGD Reference Report - Complement inhibitors selectively attenuate injury following administration of cobra venom factor to rats. - Rat Genome Database

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Complement inhibitors selectively attenuate injury following administration of cobra venom factor to rats.

Authors: Proctor, LM  Strachan, AJ  Woodruff, TM  Mahadevan, IB  Williams, HM  Shiels, IA  Taylor, SM 
Citation: Proctor LM, etal., Int Immunopharmacol. 2006 Aug;6(8):1224-32. Epub 2006 Apr 3.
RGD ID: 2303017
Pubmed: PMID:16782534   (View Abstract at PubMed)
DOI: DOI:10.1016/j.intimp.2006.03.002   (Journal Full-text)

Systemic activation of complement is a pathophysiological response common to severe disturbances such as hemorrhagic shock, major burn injury and sepsis. Intravenous infusion of cobra venom factor (CVF) has been used as an animal model of acute respiratory distress syndrome (ARDS), and reliably and selectively induces rapid intravascular activation of the complement system, leading to acute organ damage. In the present study, we have used different complement inhibitors to investigate the roles of complement products in CVF-induced responses in the rat. Rats were treated with either a C5a receptor antagonist (C5aRA, AcF-[OP(d-Cha)WR], 1 mg/kg i.v. or 10 mg/kg p.o.), a C3a receptor antagonist (C3aRA, N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine, 0.1 mg/kg i.v.) or a convertase inhibitor, rosmarinic acid (RMA, 10 mg/kg i.v.), prior to CVF-induced complement challenge. Intravenous CVF resulted in hallmark events evident in the development of ARDS, including systemic neutropenia followed by neutrophil migration to the lung and bronchoalveolar vascular leakage, blood pressure alterations, and an increase in TNFalpha levels in both serum and bronchoalveolar lavage fluid. These hemodynamic changes were differentially inhibited by antagonism of C5a receptors, C3a receptors or by inhibition of the entire complement cascade using RMA. This evidence strongly implicates complement factors in the development of lung injury associated with systemic complement activation and identifies complement inhibition as a potential therapeutic target for acute syndromes such as ARDS and other severe systemic shock states mediated by activation of complement.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
C3ar1  (complement C3a receptor 1)
C5ar1  (complement C5a receptor 1)

Genes (Mus musculus)
C3ar1  (complement component 3a receptor 1)
C5ar1  (complement component 5a receptor 1)

Genes (Homo sapiens)
C3AR1  (complement C3a receptor 1)
C5AR1  (complement C5a receptor 1)


Additional Information