Role of SR-BI in LPS detoxification--Supplement Year 5

Scavenger receptor BI (SR-BI) is an HDL receptor that regulates HDL cholesterol levels by mediating the delivery of HDL cholesterol esters to the liver. We recently report a novel and potentially clinically important function of SR-BI in protection against LPS-induced death. LPS challenge resulted in 90% fatality of SR-BI null mice, whereas all the wild type littermates survived. More importantly, using a cecum ligation and puncture (CLP) septic model, we demonstrate that CLP treatment induced 100% fatality of SR-BI null mice whereas only 28.5% fatality of wild type littermates. Our findings indicate that SR-BI is critical for survival during sepsis in mice. We hypothesize that SRBI prevents LPS-induced death by facilitating LPS clearance and suppressing inflammatory reactions. Understanding the mechanism whereby SR-BI prevents LPSinduced death will elucidate a novel mechanism for survival during sepsis and may reveal a strategy for intervention of sepsis.