Inhibition of secretory phospholipase A2 activity attenuates lipopolysaccharide-induced acute lung injury in a mouse model.
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.
Sato
Ryota
R
Department of Internal Medicine II, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Yamaga
Satoshi
S
Watanabe
Kazuyoshi
K
Hishiyama
Sensuke
S
Kawabata
Ken-ichi
K
Kobayashi
Tsuyoshi
T
Fujioka
Daisuke
D
Saito
Yukio
Y
Yano
Toshiaki
T
Watanabe
Kazuhiro
K
Watanabe
Yosuke
Y
Ishihara
Hiroshi
H
Kugiyama
Kiyotaka
K
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
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