title: Phosgene effects on F-actin organization and concentration in cells cultured from sheep and rat lung.
abstract: Pulmonary edema and immunosuppression of the lung are primary causes of debilitation and death from phosgene gas exposure. The pathophysiology that gives rise to these conditions shares a common clinical pathway. However, the target cells and lesions that disrupt normal barrier function and immune response of the lung are complex and poorly understood. Using confocal laser microscopy and FITC-conjugated phalloidin, we 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 ranging from 0.15 to 1.0 x LCt50 for sheep in vivo (3300 ppm.min) produced immediate, dose-dependent decreases in average F-actin content of cultured endothelial cells. Dense peripheral bands and stress fibers were diminished and partially disrupted but were not destroyed by these doses. Changes in ultrastructure and the permeability barrier of endothelial tissues included separation of basal lamina and development of paracellular leakage paths. Phosgene also decreased the F-actin in airway epithelial cells and potentiated phenotypic transformations that gave rise to progeny with dendritic processes. Differences in endothelial and airway epithelial response indicate that the cytoskeletal effects of phosgene were cell-type specific. Disruption of basal lamina, depletion 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-actin reorganization and appearance of dendritic cells among airway epithelial may affect other functions of the lung.
authors.affiliation: Physiology Branch, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
authors.forename: R J
authors.initials: RJ
authors.lastname: Werrlein
authors.forename: J S
authors.initials: JS
authors.lastname: Madren-Whalley
authors.forename: S D
authors.initials: SD
authors.lastname: Kirby
mesh_terms: D000199:Actins / Q000187:drug effects*; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008854:Microscopy, Electron; D009994:Osmolar Concentration; D010705:Phosgene / Q000633:toxicity*; D051381:Rats; D012756:Sheep; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000199:Actins; D010705:Phosgene