Effects of Phosgene Exposure on Lung Arachidonic Acid Metabolism

摘要

Phosgene is a pulmonary toxicant that can produce lung edema,bronchoconstriction, and immune suppression following an acute exposure. In the report, the effects of acute in vivo and in vitro phosgene exposure on lung arachidonic acid metabolism were examined. Fischer-344 rats were exposed either to air or to phosgene (0.05-1.0 ppm) for 4 hr and the lungs lavaged at 0.4, 20, and 44 hr post exposure. Leukotriene B4 (LTB4), leukotrienes C4, D4, and E4 (LTC4/D4/E4), and prostaglandin E2 (PGE2) were measured in lavage fluid by radioimmunoassay. With the exception of the LTC4/D4/E4 concentration in 1.0 ppm phosgene-exposed rats, in vivo phosgene exposure at > or = 0.1 ppm produced significant decreases in the concentrations of PGE2, LTB4, and LTC4/D4/E4 in the lavage fluid collected immediately after exposure. Temporally associated with the decreased eicosanoid production was a smaller number of alveolar macrophages recovered in the lavage fluid of phosgene-exposed rats. Dose response studies were performed. Phosgene exposure in vitro of rat and human alveolar macrophages was then performed to determine if the toxicant could directly inhibit the formation of eicosanoids by alveolar macrophages.