The immune-modulating role of scavenger receptor A (Sra) during inflammation and sepsis

The immune response is mediated by the innate and adaptive immune systems, which use secreted molecules to communicate information between cells, in particular cytokines. A delicate balance of pro- and anti-inflammatory cytokines is necessary for the proper removal of pathogens. While this inflammatory response is necessary for both normal wound healing as well as the elimination of potentially harmful stimuli, it can itself become damaging to the host if the response is not properly controlled. Innate immune cells identify generic components of foreign objects, known as Pathogen Associated Molecular Patterns (PAMPS), which are recognized by receptors called pattern recognition receptors (PRR). One of these receptors is scavenger receptor A (Sra), also coined Macrophage Specific Receptor 1 (Msrl).;Sra is a multi-ligand cell surface glycoprotein primarily expressed on macrophages, which belongs to a larger family of scavenger receptors. Sra was first discovered as a binding protein for modified low-density lipoprotein (LDL). In this regard, it was shown to be a major protein involved in the formation of foam cells and the development of atherosclerosis. While there has been significant investigation into the role of Sra in lipid metabolism, less is known about the exact function of Sra in regulating the immune response during injury or infection. Previous studies from our laboratory have shown that Sra is a modifier gene for the expression of interleukin 10 (IL-10) after exposure to bacterial lipopolysaccharide (LPS). The present work explores the role of Sra in modulating the inflammatory response under sepsis-like conditions.;Sepsis is a major health problem in the United States that affects more than three-quarters of a million people every year. It is likely the product of a prolonged and uncontrolled inflammatory response. In my studies, I investigated the immune-modulating role that Sra plays in two separate models of sepsis: cecal ligation and puncture (CLP) and endotoxemia. Results from this body of work support previous findings of Sra's immune modulating role of IL-10 expression. In addition, we identified a novel association of Sra with acute acalculous cholecystitis during sepsis. Furthermore, we have provided novel information on the link between Sra, cholesterol and sepsis.