PULMONARY IMMUNOTOXICITY OF INHALED AMMONIUM METAVANADATE IN FISHER-344 RATS

Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m(3) (as ammoniu m metavanadate NH4VO3, 0.32 mu m MMD) atmospheres for 8 hr/day for 4 d ays in a nose-only exposure system. In exposed rats, lung V burdens in creased 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 an d small macrophages (Mo), as well as levels of lavageable protein and lactate dehydrogenase, were significantly elevated as compared with le vels observed with air-exposed rats. Vanadium also affected pulmonary alveolar Mo (PAM) capacities to produce and respond to immunoregulatin g cytokines. Inducible PAM production of tumor necrosis factor-alpha w as significantly inhibited, as was the ability to increase cell surfac e Class II/I-A molecule expression in response to interferon-gamma (IF N gamma). PAM from V-exposed hosts were also inhibited ire their abili ty to be primed by IFN gamma to produce superoxide anion and hydrogen peroxide in response to stimulation with opsonized zymosan. These stud ies indicate that short-term repeated exposure of rats to atmospheric V, at levels encountered in an occupational setting, can alter host pu lmonary immunomocompetence, with one major effect occurring at the lev el of cytokine-related functions, These alterations map be underlying mechanisms for the well-documented increases in bronchopulmonary infec tions and cancers in workers chronically exposed to V-containing atmos pheres. (C) 1996 Society of Toxicology.