Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice

Mammals possess various types of secretory phospholipase A(2), which differ in the primary structure and tissue distribution. The phosholipase A(2) receptor (PLA(2)R) recognizes group IB phospholipase A(2) (PLA(2)-IB) and mediates the PLA(2)-IB-induced biological responses in non-digestive organs, including eicosanoid production and contraction of airway smooth muscles. In this study, we generated PLA(2)R-deficient mice to define its biological roles further. These mice are viable, fertile, and without evident histopathological abnormalities. There was no difference in the clearance of circulating PLA(2)-IB between wild-type and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA(2)-R-deficient mice exhibited longer survival than wild-type mice. The mutant mice were also resistant to lethal effects of exogenous PLA(2)-IB after sensitization with sublethal dose of LPS. The plasma levels of tumor necrosis factor-alpha and interleukin-1 beta elevated after LPS treatment were significantly reduced in mutant mice compared with wild-type mice. These findings suggest a potential role of PLA(2)R in the progression of endotoxic shock.