Development of assays to monitor functions of alveolar macrophages, neutrophils, and type-II epithelial cells, to characterize variables which modify phagocytic activity of alveolar macrophages and neutrophils, to construct dose response curves for macrophages exposed to crystalline silica (14808607), and to test response of neutrophils to a possible mediator were reported. Assays were developed to monitor membrane integrity, viability, phagocytic activity, and oxidant release by macrophages. Viability and oxidant release in neutrophils were successfully assayed, along with water movement, surfactant synthesis, and xenobiotic metabolism of type-II cells. Release of potentially harmful oxidants and lysosomal enzymes from macrophages resulted from in-vitro silica exposure. Intratracheal instillation of silica activated oxidant production by macrophages. Silica could become coated with surfactants making it less toxic. Formation of radicals on the surface of freshly cut quartz contributed to overall toxicity. No change in-vivo was noted in activity of cytochrome-P450 enzymes in type-II cells. Tetrandrine, an antifibrosis drug, inhibited production of oxidants by macrophages and was effective in-vitro and in-vivo. Activity of leukocytes and macrophages was enhanced by platelet activating factor, suggesting a role in stimulating release of oxidants. Toxicities of coal dust, diesel exhaust, cotton dust, mycotoxins, asbestos (1332214), wollastonite (13983170), and metal ions were also determined.
Biochemistry Section, NIOSH, U.S. Department of Health and Human Services, 31 pages, 82 references