The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

The macrophage scavenger receptor (SR-A) is a multifunctional receptor that is associated with several important pathological conditions, including atherosclerosis. In this study, we show, using a sterile peritonitis model, that it can regulate the inflammatory response. SR-A null mice display an increased initial granulocytic infiltration because of overproduction of the CXC chemokines, MIP-2 and keratinocyte-derived cytokine. This differential response is dependent upon particle internalization and can be mimicked by advanced glycation end product-BSA-conjugated latex beads. Thus SR-A is a nonactivating receptor, which is the first example of a pattern recognition receptor that serves to counter the activities of proinflammatory receptors and attenuates the production of specific chemokines to ensure an inflammatory response of the appropriate magnitude.