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Inhibition of Phospholipase A<SUB>2</SUB> Diminishes the Acute Alveolar Injury Induced by Interleukin-1&#12545;

Inhibition of Phospholipase A<SUB>2</SUB> Diminishes the Acute Alveolar Injury Induced by Interleukin-1&#12545;

<P> In an attempt to investigate the role of phospholipase A<SUB>2</SUB>(PLA<SUB>2</SUB>) in interleukin-1 (IL-1) induced acute lung injury, mepacrine was tried to inhibit PLA<SUB>2</SUB> in IL-1 induced ARDS rats. For confirmation of acute lung injury by IL-1, and to know the role of neutrophils in this injury, lung leak index, lung myeloperoxidase(MPO), number of neutrophils and protein content in the bronchoalveolar lavage (BAL) and wet lung weight were measured. At the same time lung PLA<SUB>2</SUB> was measured to know the effect of IL-1 on PLA<SUB>2</SUB> activity. Pulmonary surfactant was also measured for an investigation of type II alveolar cell function. Neutrophil adhesion assay was performed to know the effect of PLA<SUB>2</SUB> inhibition <I>in vitro</I> with human umbilical vein endothelial cells (HUVEC). For precise location of injury by IL-1, morpholgical study was performed by electron microscopy. Five hours after instillation of IL-1 (50 ng/rat), lung leak index, protein content, number of neutrophils, lung MPO and wet lung weight were increased significantly. Five hours after IL-1 instillation lung PLA<SUB>2</SUB> activity was increased significantly, and increased surfactant release was observed in IL-1 induced ARDS rats BAL. In contrast, in rats given mepacrine and IL-1, there was decrease of acute lung injury i.e. decrease of lung leak index, wet lung weight, protein content, number of neutrophils in BAL and decreased lung MPO activity. Mepacrine decreased surfactant release also. Interestingly, inhibition of PLA<SUB>2 </SUB>decreased adhesion of human neutrophils to HUVEC <I>in vitro.</I> Morphologically, IL-1 caused diffuse necrosis of endothelial cells, type I and II epithelial cells and increased the infiltration of neutrophils in the interstitium of the lung but after mepacrine treatment these pathological findings were lessened. On the basis of these experimental results it is suggested that PLA<SUB>2</SUB> has a major role in the pathogenesis of acute lung injury mediated by neutrophil dependent manner in IL-1 induced acute lung injury.

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