Scavenger Receptor Class A Plays a Central Role in Mediating Mortality and the Development of the Pro- Inflammatory Phenotype in Polymicrobial Sepsis

Sepsis is a frequent complication in critical illness. The mechanisms that are involved in initiation and propagation of the disease are not well understood. Scavenger receptor A (SRA) is a membrane receptor that binds multiple polyanions such as oxidized LDL and endotoxin. Recent studies suggest that SRA acts as a pattern recognition receptor in the innate immune response. The goal of the present study was to determine the role of SRA in polymicrobial sepsis. SRA deficient (SRA2/2) and C57BL/6JB/6J (WT) male mice were subjected to cecal ligation and puncture (CLP) to induce polymicrobial sepsis. NFkB activity, myeloperoxidase activity, and co-association of SRA with toll like receptor (TLR) 4 and TLR2 was analyzed in the lungs. Spleens were analyzed for apoptosis. Serum cytokines and chemokines were assayed. Blood and peritoneal fluid were cultured for aerobic and anaerobic bacterial burdens. Long term survival was significantly increased in SRA2/2 septic mice (53.6 % vs. 3.6%, p,0.05) when compared to WT mice. NFkB activity was 45.5 % lower in the lungs of SRA2/2 septic mice versus WT septic mice (p,0.05). Serum levels of interleukin (IL)-5, IL-6, IL-10 and monocyte chemoattractant protein 2