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  • Title: Natural killer activity in Fischer-344 rat lungs as a method to assess pulmonary immunocompetence: immunosuppression by phosgene inhalation.
    Author: Burleson GR, Keyes LL.
    Journal: Immunopharmacol Immunotoxicol; 1989; 11(2-3):421-43. PubMed ID: 2621324.
    Abstract:
    Phosgene, also known as carbonyl chloride, carbon oxychloride, and chloroformyl chloride, is a toxic air pollutant and a potential occupational health hazard. Studies were initiated (a) to evaluate the measurement of pulmonary natural killer (NK) activity as a method to assess pulmonary immunocompetence, and (b) to determine whether exposure to phosgene resulted in local pulmonary or systemic immune dysfunction. Fischer-344 male rats were exposed either to filtered air or to 1.0 ppm phosgene gas for four hours. The effect of phosgene on lung NK activity was quantified at different times after acute phosgene exposure. Pulmonary NK activity was measured by mincing lung tissue into small pieces prior to incubation with collagenase. Whole-lung homogenate was assayed for NK activity utilizing a 4 hour 51-Cr-release assay with YAC-1 cells as target cells. Acute phosgene exposure resulted in a suppressed pulmonary NK activity on days 1, 2, and 4 after exposure; however, normal levels of biological activity were observed 7 days after exposure. The suppressed NK activity was not restored after removal of adherent cells from the lung homogenate, thus indicating that the effect of phosgene on NK activity was not due to immunosuppression via mobilization of suppressor alveolar macrophages. Pulmonary immunotoxicity was also observed after exposure at 0.5 ppm, while no adverse effects were observed at 0.1 ppm phosgene. Systemic immunotoxic effects were observed for NK activity in the spleen, but not in the peripheral blood. It is thus important in pulmonary immunotoxicology to evaluate systemic immune functions, since secondary effects--distant to the original interaction--may occur with potentially serious consequences. Cells exhibiting natural killer activity comprise a part of the nonspecific innate immunity that is important in defense against both neoplastic and viral diseases. Any perturbation of this important nonspecific immunological mechanism may result in a compromised host more susceptible to infectious and neoplastic disease.
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