PHOSGENE EFFECTS ON F-ACTIN ORGANIZATION AND CONCENTRATION IN CELLS CULTURED FROM SHEEP AND RAT LUNG

Pulmonary edema and immunosuppression of the lung are primary causes o f debilitation and death from phosgene gas exposure. The pathophysiolo gy that gives rise to these conditions shares a common clinical pathwa y. However, the target cells and lesions that disrupt normal barrier f unction and immune response of the lung are complex and poorly underst ood. Using confocal laser microscopy and FITC-conjugated phalloidin, w e have studied the effects of phosgene on F-actin in endothelial cells from sheep pulmonary arteries and epithelial cells from rat tracheal explants. Image analyses from attached culture systems indicate that F -actin was a sensitive target molecule in both species. Exposures rang ing from 0.15 to 1.0 x LCt(50) for sheep in vivo (3300 ppm.min) produc ed immediate, dose-dependent decreases in average F-actin content of c ultured endothelial cells. Dense peripheral bands and stress fibers we re diminished and partially disrupted but were not destroyed by these doses. Changes in ultrastructure and the permeability barrier of endot helial tissues included separation of basal lamina and development of paracellular leakage paths. Phosgene also decreased the F-actin in air way epithelial cells and potentiated phenotypic transformations that g ave rise to progeny with dendritic processes. Differences in endotheli al and airway epithelial response indicate that the cytoskeletal effec ts of phosgene were cell-type specific. Disruption of basal, lamina, d epletion of F-actin, and development of endothelial leakage paths may contribute to decreased barrier function and increased permeability of vascular tissues. Phosgene-induced transformations that involved F-ac tin reorganization and appearance of dendritic cells among airway epit helia may affect other functions of the lung.