Abstract 5542: Role of Scavenger Receptor BI in Sepsis
Scavenger receptor BI (SR-BI) is a well-established HDL receptor that regulates plasma HDL cholesterol levels by selectively uptake cholesterol ester from HDL. We recently reported a novel function of SR-BI namely protection against endotoxin-induced animal death. Using a lipopolysaccharides (LPS) induced endotoxic animal model, we found that LPS challenge induced 90% fatality of SR-BI null mice while all the wild type littermates survived, indicating that SR-BI plays a pivotal role in protection against LPS toxicity in vivo. In the current studies, we determined whether SR-BI plays a protective role in sepsis using an established septic animal model (cecal ligation and puncture, CLP). We demonstrate that CLP treatment induced 100% fatality of SR-BI null mice (n=20) whereas only 21% fatality of wild type littermates (n=27) and 36% fatality of heterozygous littermates (n=30). Moreover, SR-BI null mice exhibited exaggerated and prolonged inflammatory response as shown by elevated proinflammatory cytokine levels in serum upon CLP treatment compared to wild type littermates. Further studies revealed that the plasma LPS levels were significantly higher in SR-BI null mice compared to wild type control mice, indicating that SR-BI is required for LPS clearance in sepsis. Our findings clearly demonstrate that SR-BI is a critical protective modulator in sepsis in mice, which may reveal a novel target for the intervention of sepsis.
(Supported by grant from American Heart Association 0530241N)
This research has received full or partial funding support from the American Heart Association, AHA National Center.