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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.