title: Inhibition of secretory phospholipase A2 activity attenuates lipopolysaccharide-induced acute lung injury in a mouse model.
abstract: This study evaluated the hypothesis that LY374388, an inhibitor of secretory phospholipase A(2) (sPLA(2)) activity, may exert a protective effect on lipopolysaccharide (LPS)-induced acute lung injury in male C57BL/6J mice. Intratracheal administration of LPS increased histopathological changes in lung tissue, lung wet to dry ratios, and the bronchoalveolar lavage fluid levels of neutrophil numbers, sPLA(2) activity, leukotriene B(4), and thromboxane B(2). However, a simultaneous intraperitoneal treatment with LY374388 significantly attenuated these LPS-induced changes. Thus, inhibition of sPLA(2) activity significantly attenuated the acute lung injury induced by LPS. sPLA(2) played an important role in the pathogenesis of LPS-induced acute lung injury in mice.
authors.affiliation: Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Sato
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaga
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Sensuke
authors.initials: S
authors.lastname: Hishiyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yano
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishihara
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004353:Drug Evaluation, Preclinical; D007210:Indoleacetic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000032:analysis; D008070:Lipopolysaccharides; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology; D009195:Peroxidase / Q000378:metabolism; D054497:Phospholipases A2, Secretory / Q000032:analysis / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000032:analysis
chemical_list: C551333:(3-aminooxalyl-1-benzyl-2-ethyl-6-methyl-1H-indol- 4-yloxy)-acetic acid methyl ester; D007210:Indoleacetic Acids; D008070:Lipopolysaccharides; D007975:Leukotriene B4; D013929:Thromboxane B2; D009195:Peroxidase; D054497:Phospholipases A2, Secretory