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Abstract
Phosgene can acylate macromolecules and may react with and affect enzymes involved in arachidonic acid metabolism. We examined the effects of an acute phosgene exposure in vivo and in vitro on lung arachidonic acid metabolism. Fischer 344 rats were exposed either to air or to phosgene (0.05–7.0 ppm) for 4 h and the lungs were lavaged at 0, 4, 20, and 44 h postexposure. Leukotriene B, (LTBJ, peptide leuko-trienes C4 D4 and E4 (LTC4/D/E4, and prostaglandin E2 (PCE2) were measured in la-vage fluid by radioimmunoassay Phosgene exposure in vivo (0.7–7.0 ppm for 4 b) produced significant decreases in concentrations of PGE, (maximal decrease of 74%), LTB, (maximal decrease of 59%), and LTC4/D4/E4 (maximal decrease of 97%) measured in rat lavage fluid immediately postexposure. Associated with this decrease in eicosa-noid production was a decrease in the number of alveolar macrophages and an increased number of neutrophils recovered in the lavage fluid of phosgene-exposed rats. Lung lavage eicosanoid concentrations in rats exposed to either 0.7 or 0.25 ppm phosgene returned to or exceeded air control values by 44 h postexposure. However, rats exposed to 0.5 or 7.0 ppm phosgene had a persistent decrease in the concentration of PGE, and LTC4/D4/E4 at44h after the exposure. Phosgene exposure in vitro (7.0 ppm for 4 h) of rat or human alveolar macrophages induced a 56% decrease in the production of LTB4 in the rat macrophages and a 31% nonsignificant decrease in the formation of LTB4 in human alveolar macrophages. Production of PCE, and the LTC4/D4/E4 by the rat macrophages, and PCE2 by the human macrophages, was not different from air-exposed culture values. These data suggested that phosgene exposure altered arachidonic acid metabolism in rat lungs after in vivo exposure and in rat and human alveolar macrophages after exposure in vitro. These changes in lung mac-rophage arachidonic acid metabolism may be involved in some of the lung responses to phosgene exposure.