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 A₂ (sPLA₂) 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, sPLA₂ activity, leukotriene B₄, and thromboxane B₂. However, a simultaneous intraperitoneal treatment with LY374388 significantly attenuated these LPS-induced changes. Thus, inhibition of sPLA₂ activity significantly attenuated the acute lung injury induced by LPS. sPLA₂ played an important role in the pathogenesis of LPS-induced acute lung injury in mice.

KEYWORDS :

• acute lung injury
• acute respiratory distress syndrome
• eicosanoids
• inhibitor
• lipopolysaccharide
• phospholipase A₂