||Reduction of Neutrophil Influx Diminishes Lung Injury and Mortality Following Phosgene Inhalation.
Ghio, A. J. ;
Kennedy, T. P. ;
Hatch, G. E. ;
Tepper, J. S. ;
||Duke Univ. Medical Center, Durham, NC. Div. of Allergy, Critical Care, and Respiratory Medicine. ;ManTech Environmental Technology, Inc., Research Triangle Park, NC.;Health Effects Research Lab., Research Triangle Park, NC. Inhalation Toxicology Div.
Air pollution effects(Animals) ;
Pulmonary edema ;
Arachidonate 5-lipoxygenase ;
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Phosgene inhalation causes a severe noncardiogenic pulmonary edema characterized by an influx of neutrophils into the lung. To study the role of neutrophils in lung injury and mortality after phosgene, the authors investigated the effects of leukocyte depletion with cyclophosphamide, inhibiting the generation of the chemotaxin leukotriene B4 by 5-lipoxygenase inhibitor AA861, and impairing neutrophil migration with the microtubular poison colchicine. Cyclophosphamide, 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 (0.5 ppm x 60 min.). Cyclophosphamide, AA861, and colchicine also significantly decreased mortality from phosgene (2.0 ppm x 90 min.) in mice. Colchicine significantly reduced neutrophil influx, lung injury and mortality even when given 30 minutes after phosgene exposure. The authors conclude that lung injury and mortality after phosgene exposure are associated with an influx of neutrophils into the lung. Preventing neutrophil migration with colchicine may hold therapeutic potential in phosgene poisoning.