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Vanadium-induced pulmonary inflammation and apoptosis in mice.

Wang L; Medan D; Huang C; Shi X; Mercer RR; Millecchia L; Castranova V; Rojanaskul Y
Toxicologist 2002 Mar; 66(1-S):354
Pulmonary exposure to vanadium and vanadium-containing compounds is associated with acute pulmonary inflammation, characterized by a rapid influx of polymorphonuclear neutrophils with a peak response at 6 h and resolution by 3 d. Sodium metavanadate [V (V)] can induce cell apoptosis in vitro, but little is known about relationship of V (V) and lung cell apoptosis in vivo. We hypothesized that vanadium may induce lung cell apoptosis through reactive oxygen species (ROS) in vivo and neutrophil apoptosis is involved in the resolution of vanadium-induced lung inflammation. To test this hypothesis, mice were treated with V (V) or saline control, and the bronchoalveolar lavage (BAL) cells were examined at various times for short-lived free radicals by electron spin resonance (ESR) and for apoptosis using terminal deoxyribonucleotidyl transferase-mediated nick end labeling (TUNEL). Control mouse BAL cells showed no significant free radical activity and only resident alveolar macrophages in the BAL fluids with no evidence of apoptosis. In contrast, V (V) induced a greater level of free radicals and caused apoptosis of BAL cells which are predominantly neutrophils. Catalase blocked both free radical generation and apoptosis induced by V (V). The number of apoptotic cells gradually increased and reached a maximal level by 24 h where it subsequently declined. After 24 h when the vanadium-induced lung inflammation was in the resolution phase, we observed an increased influx of macrophages and their engulfment of apoptotic bodies in the BAL fluid. At 72 h when the total number of neutrophils fell to the baseline level, remnants of apoptotic bodies could still be seen in the cytoplasm of macrophages. We conclude that (1): ROS, like H2O2, are one of causes of apoptosis induced by vanadium; (2): apoptosis of neutrophils and clearance by macrophages is an important mechanism in the resolution of vanadium-induced lung inflammation.
Pulmonary-disorders; Pulmonary-system-disorders; Animal-studies; Vanadium-compounds; In-vivo-studies; Lung-cells; Respiratory-system-disorders
Publication Date
Document Type
Fiscal Year
NIOSH Division
Priority Area
Work Environment and Workforce: Mixed Exposures
Source Name
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee
Page last reviewed: March 3, 2021
Content source: National Institute for Occupational Safety and Health Education and Information Division