Scavenger receptor BI prevents septic death

Abstract

Scavenger receptor BI (SR‐BI) is a HDL receptor which 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 (cecum ligation and puncture, CLP). We demonstrate that CLP treatment induced 100% fatality of SR‐BI null mice within three days (n=20) whereas only 21% fatality of wild type littermates (n=27) and 36% fatality of heterozygous littermates (n=30). 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 grants from American Heart Association 0530241N and from the NIH 2P20RR015592)