© 1996 Oxford University Press
research-article |
Pulmonary Immunotoxicity of Inhaled Ammonium Metavanadate in Fisher 344 Rats
Department of Environmental Medicine, New York University Medical Center Long Meadow Road, Tuxedo, New York, 10987
Received March 1, 1996; accepted July 30, 1996
Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m3 (as ammonium metavanadate NH4VO3, 0.32 µm MMD) atmospheres for 8 hr/day for 4 days in a nose-only exposure system. In exposed rats, lung V burdens increased in a time-dependent fashion. Analysis of lung cells and lavage fluid 24 hr after the final exposure suggested that tissue damage and a strong inflammatory response was elicited; numbers of neutrophil and small macrophages (Mø), as well as levels of lavageable protein and lactate dehydrogenase, were significantly elevated as compared with levels observed with air-exposed rats. Vanadium also affected pulmonary alveolar Mø (PAM) capacities to produce and respond to immunoregulating cytokines. Inducible PAM production of tumor necrosis factor-a was significantly inhibited, as was the ability to increase cell surface Class II/I-A molecule expression in response to interferon-
(rFN-). PAM from V-exposed hosts were also inhibited in their ability to be primed by EFN- to produce superoride anion and hydrogen peroxide in response to stimulation with opsonized zy-mosan. These studies indicate that short-term repeated exposure of rats to atmospheric V, at levels encountered in an occupational setting, can alter host pulmonary immunomocompetence, with one major effect occurring at the level of cytokine-related functions. These alterations may be underlying mechanisms for the well-documented increases in bronchopulmonary infections and cancers in workers chronically exposed to V-containing atmospheres.