Phospholipase A2 mediates nitric oxide production by alveolar macrophages and acute lung injury in pancreatitis.
AUTOR(ES)
Tsukahara, Y
RESUMO
OBJECTIVE: Reportedly, nitric oxide (NO) derived from alveolar macrophages (AMs) and increased serum phospholipase A2 (PLA2) activity are associated with the pathogenesis of lung injury in acute pancreatitis. The authors examined the possibility that PLA2 causes, in part, the induction of NO production by AMs in pancreatitis. METHODS: Pancreatitis was induced in rats by selective pancreatic duct ligation (SPL). AMs were stimulated with PLA2 or SPL rat serum, with or without administration of the PLA2 inhibitor quinacrine. Then NO production from the AMs was measured by the Griess method, inducible NO synthase mRNA expression of AMs was analyzed by the reverse transcription-polymerase chain reaction, and cytotoxic effects of AMs on human umbilical vein endothelial cells was examined by a 51Cr release assay. In vivo, the effect of quinacrine on lung injury was determined by measuring the arterial blood oxygen pressure (PaO2), lung weight, and lung permeability using Evans blue dye concentration of SPL rat. RESULTS: In vitro, the serum with high PLA2 activity induced NO production by rat AMs. PLA2 (50 ng/ml) induced significant amounts of NO production, inducible NO synthase mRNA expression, and cytotoxicity toward the human umbilical vein endothelial cells in normal rat AMs, and these activities were significantly inhibited by quinacrine. In vivo, rats with pancreatitis that were given quinacrine showed decreased concentrations of NO2- and NO3- in the bronchoalveolar lavage fluid, and the PaO2, lung edema, and lung permeability were improved significantly. CONCLUSION: PLA2 induces AMs to release NO, which contributes to lung injury in acute pancreatitis. This lung injury was prevented by the administration of the PLA2 inhibitor quinacrine.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1191704Documentos Relacionados
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