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REDUCTION OF NEUTROPHIL INFLUX DIMINISHES LUNG INJURY AND MORTALITY FOLLOWING PHOSGENE INHALATION
Citation:
Ghio, A., T. Kennedy, G. Hatch, AND J. Tepper. REDUCTION OF NEUTROPHIL INFLUX DIMINISHES LUNG INJURY AND MORTALITY FOLLOWING PHOSGENE INHALATION. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/300.
Description:
Phosgene inhalation causes a sever noncardiogenic pulmonary edema characterized by an influx of neutrophils into the lung. o study the role of neutrophils in lung injury and mortality after phosgene, we investigated the effects of leukocyte depletion with cyclophosphamide, inhibiting the generation of the chemotaxis leukotriene B4 by 5-lipoxygenase inhibitor AA861, and impairing neutrophil migration with the microtubular poison colchicine. yclophosphamide, AA861 and colchicine injected before exposure significantly reduced percent neutrophils, protein and thiobarbituric acid reactive products in bronchoalveolar lavage fluid of rats exposed to phosgene (0.r ppm x 60 min.). yclophosphamide, AA861, and colchicine also significantly decreased mortality from phosgene (2.0 ppm x 90 min.) in mice. olchicine significantly reduced neutrophil influx, lung injury and mortality even when given 30 minutes after phosgene exposure. e conclude that lung injury and mortality after phosgene exposure are associated with an influx of neutrophils into the lung. reventing neutrophil migration with colchicine may hold therapeutic potential in phosgene poisoning.