Pulmonary immunotoxicity of inhaled ammonium metavanadate in Fisher 344 rats.
Male Fisher 344 rats were exposed to 2 mg vanadium(V)/m3 (as ammonium metavanadate NH4VO3, 0.32 micron 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-alpha was significantly inhibited, as was the ability to increase cell surface Class II/I-A molecule expression in response to interferon-gamma (IFN gamma). PAM from V-exposed hosts were also inhibited in their ability to be primed by IFN gamma to produce superoxide anion and hydrogen peroxide in response to stimulation with opsonized zymosan. 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.
Cohen
M D
MD
Department of Environmental Medicine, New York University Medical Center, Tuxedo 10987, USA.
Yang
Z
Z
Zelikoff
J T
JT
Schlesinger
R B
RB
D000280:Administration, Inhalation; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species; D014638:Vanadates / Q000008:administration & dosage / Q000633:toxicity*
D000395:Air Pollutants, Occupational; D017382:Reactive Oxygen Species; D014638:Vanadates; C101036:ammonium metavanadate