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EFFECTS OF PHOSGENE EXPOSURE ON LUNG ARACHIDONIC ACID METABOLISM
Citation:
Madden, M., M. Friedman, L. Keyes, H. Koren, AND G. Burleson. EFFECTS OF PHOSGENE EXPOSURE ON LUNG ARACHIDONIC ACID METABOLISM. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/007 (NTIS PB91177352), 1991.
Description:
Phosgene is a pulmonary toxicant that can produce lung edema, bronchoconstriction, and immune suppression following an acute exposure. he response of the lung to phosgene inhalation may be mediated through alternations in the metabolism of arachidonic acid to the biologically potent prostagladins and leukotriences. n this report, we examined he effects of acute in vivo and in vitro phosgene exposure on lung arachidonic acid metabolism. ischer-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, 2-, and 44 hr post exposure. eukotriene B4 (LTB4), leukotrienes C4, D4, and E4 (LTC4/D$/E4), and prostaglandin E2 (PGE2) were measured in lavage fluid by radioimmunoassay, ith 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 (maximal inhibition of 74%), LTB4 (Maximal inhibition of 59%)< and LTC4/D4/E4 (maximal inhibition of 97%) in the lavage fluid collected immediately after exposure. emporally associated with the decreased eicosanoid production was a smaller number of alveolar macrophages recovered in the lavage fluid of phosgene-exposed rats. ose response studies were performed. hosgene 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. n vitro exposure of rat macrophages to 1.0 ppm phosgene (4 hr) caused a 56% decrease in the production of LTB4, and a 31% decrease in the formation of LTB4 by human macrophages. roduction of PGE2 and the peptide leukotrienes by the rat alveolar macrophage, and PGE2 by the human alveolar macrophage, was not different from air-exposed culture values. hese data suggested that in vitro phosgene exposure inhibited the LTB4 production of alveolar macrophages, but that other mechanisms, e.g., the loss of alveolar macrophages from the lungs, may be responsible for the decreased formation of PGE2 and LTC4/D4/E4 observed in vitro.
