RESISTANCE TO ENDOTOXIC-SHOCK IN PHOSPHOLIPASE A(2) RECEPTOR-DEFICIENT MICE

Mammals possess various types of secretory phospholipase A(2), which d iffer in the primary structure and tissue distribution. The phosholipa se 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 m ice to define its biological roles further. These mice are viable, fer tile, and without evident histopathological abnormalities. There was n o difference in the clearance of circulating PLA(2)-IB between wild-ty pe and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA(2)-R-deficient mice exhibited longer survival than wild-typ e mice. The mutant mice were also resistant to lethal effects of exoge nous PLA(2)-IB after sensitization with sublethal dose of LPS. The pla sma levels of tumor necrosis factor-alpha and interleukin-1 beta eleva ted after LPS treatment were significantly reduced in mutant mice comp ared with wild-type mice. These findings suggest a potential role of P LA(2)R in the progression of endotoxic shock.