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: Ryota Sato, Satoshi Yamaga, Kazuyoshi Watanabe, Sensuke Hishiyama, Ken-ichi Kawabata, Tsuyoshi Kobayashi, Daisuke Fujioka, Yukio Saito, Toshiaki Yano, Kazuhiro Watanabe, Yosuke Watanabe, Hiroshi Ishihara, Kiyotaka Kugiyama
• Journal: Experimental lung research (Exp Lung Res) Vol. 36 Issue 4 Pg. 191-200 (May 2010) ISSN: 1521-0499 [Electronic] England
• PMID: 20426527 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (3-aminooxalyl-1-benzyl-2-ethyl-6-methyl-1H-indol- 4-yloxy)-acetic acid methyl ester
• Indoleacetic Acids
• Lipopolysaccharides
• Leukotriene B4
• Thromboxane B2
• Peroxidase
• Phospholipases A2, Secretory

Topics

• Acute Lung Injury (pathology, prevention & control)
• Animals
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Drug Evaluation, Preclinical
• Indoleacetic Acids (pharmacology, therapeutic use)
• Leukotriene B4 (analysis)
• Lipopolysaccharides
• Lung (enzymology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Neutrophils (cytology)
• Peroxidase (metabolism)
• Phospholipases A2, Secretory (analysis, antagonists & inhibitors)
• Thromboxane B2 (analysis)