Role of macrophage scavenger receptor in endotoxin shock

Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages, including CD14 and macrophage scavenger receptor class A types I and II (MSR‐A), and stimulates macrophages to release various inflammatory mediators. MSR‐A recognizes a broad range of polyanionic ligands such as chemically modified lipoproteins, LPS of Gram‐negative bacteria, and lipoteichoic acid of Gram‐positive bacteria, suggesting a role in host defence. In this study, mice lacking MSR‐A were used to elucidate the role of MSR‐A in endotoxin shock. Peritoneal macrophages from MSR‐A‐deficient (MSR‐A−/−) mice bound less remarkably to LPS than those from wild‐type (MSR‐A+/+) mice and the binding activity of MSR‐A+/+ macrophages to LPS was reduced by the addition of an anti‐MSR‐A antibody. Clearance of LPS in serum was retarded in MSR‐A−/− mice after intraperitoneal administration of LPS. LPS‐induced expression of cytokines in the liver was similar in MSR‐A+/+ and MSR‐A−/− mice, but levels of interleukin (IL)‐1β expression and serum IL‐1β were lower in MSR‐A−/− mice. Administration of large doses of LPS resulted in a higher mortality of MSR‐A+/+ mice and pretreatment with an IL‐1 receptor antagonist reduced the mortality. Thus, MSR‐A‐mediated macrophage activation plays a negative role in protecting mice from endotoxin shock by enhancing IL‐1β production by macrophages. Copyright © 2000 John Wiley & Sons, Ltd.