Role of neutrophil apoptosis in vanadium-induced pulmonary inflammation in mice.
Wang-L; Medan-D; Mercer-R; Shi-X; Huang-C; Castranova-V; Din-M; Rojanasakul-Y
J Environ Pathol Toxicol Oncol 2002; 21(4):343-350
Pulmonary exposure to airborne vanadium and vanadium-containing compounds is associated with acute pulmonary inflammation, characterized by a rapid influx of neutrophilic polymorphonuclear leukocytes with a peak response at 6 hours and resolution by 3 days. We hypothesized that neutrophil apoptosis is involved in the resolution of vanadium-induced lung inflammation. To test this hypothesis, mice were exposed to inspired vanadium or saline control and the bronchoalveolar lavage (BAL) cells were examined at various times for apoptosis using terminal deoxyribonucleotidyl transferase-mediated nick end labeling (TUNEL). Control mice showed only resident alveolar macrophages in the BAL with no evidence of apoptosis. In contrast, vanadium-treated mice showed clear apoptosis of BAL cells, which were predominantly neutrophils. The number of apoptotic cells gradually increased and reached a maximal level by 24 hours with subsequent decline. After 24 hours, when the vanadium-induced lung inflammation was in the resolution phase, we observed an increased number of alveolar macrophages in BAL and the engulfment of apoptotic bodies by these macrophages. At 72 hours, the total number of neutrophils in BAL fell to the baseline level, and the number of apoptotic cells was reduced. Clearance of the apoptotic product was demonstrated by the presence of apoptotic bodies in the cytoplasm of alveolar macrophages. We conclude that apoptosis of neutrophils and clearance by alveolar macrophages are important mechanisms in the resolution of vanadium-induced lung inflammation.
Neutrophils; Vanadium-compounds; Pulmonary-system; Alveolar-cells; Leukocytes; Airborne-particles; Laboratory-animals; Animal-studies; Animals; Exposure-levels; Lung-irritants; Respiratory-system-disorders; Aerosols
Liying Wang, MD, Ph D, National Institute for Occupational Safety and Health, Pathology and Physiology Branch, 1095 Willowdale Road, Morgantown, WV 26505
Work Environment and Workforce: Mixed Exposures
Journal of Environmental Pathology, Toxicology, and Oncology