title: Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice.
abstract: Mammals possess various types of secretory phospholipase A2, which differ in the primary structure and tissue distribution. The phosholipase A2 receptor (PLA2R) recognizes group IB phospholipase A2 (PLA2-IB) and mediates the PLA2-IB-induced biological responses in non-digestive organs, including eicosanoid production and contraction of airway smooth muscles. In this study, we generated PLA2R-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 PLA2-IB between wild-type and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA2R-deficient mice exhibited longer survival than wild-type mice. The mutant mice were also resistant to lethal effects of exogenous PLA2-IB after sensitization with sublethal dose of LPS. The plasma levels of tumor necrosis factor-alpha and interleukin-1beta elevated after LPS treatment were significantly reduced in mutant mice compared with wild-type mice. These findings suggest a potential role of PLA2R in the progression of endotoxic shock.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, Osaka 553, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hanasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yokota
authors.forename: J
authors.initials: J
authors.lastname: Ishizaki
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: H
authors.initials: H
authors.lastname: Arita
mesh_terms: D000818:Animals; D005260:Female; D007375:Interleukin-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009569:Nitric Oxide / Q000097:blood; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000502:physiology; D054507:Receptors, Phospholipase A2; D012772:Shock, Septic / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; C516357:Pla2r1 protein, mouse; D011956:Receptors, Cell Surface; D054507:Receptors, Phospholipase A2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide