title: Vanadium-induced apoptosis and pulmonary inflammation in mice: Role of reactive oxygen species.
abstract: Pulmonary exposure to metals and metal-containing compounds is associated with pulmonary inflammation, cell death, and tissue injury. The present study uses a mouse model to investigate vanadium-induced apoptosis and lung inflammation, and the role of reactive oxygen species (ROS) in this process. Aspiration of the pentavalent form of vanadium, V (V), caused a rapid influx of polymorphonuclear leukocytes into the pulmonary airspace with a peak inflammatory response at 6 h post-exposure and resolution by 72 h. During this period, the number of apoptotic lung cells which were predominantly neutrophils increased considerably with a peak response at 24 h accompanied by no or minimum necrosis. After 24 h when the V (V)-induced inflammation was in the resolution phase, an increased influx of macrophages and engulfment of apoptotic bodies by these phagocytes was observed, supporting the role of macrophages in apoptotic cell clearance and resolution of V (V)-induced lung inflammation. Electron spin resonance (ESR) studies using lavaged alveolar macrophages showed the formation of ROS, including O(2)(*-), H(2)O(2), and (*)OH radicals which were confirmed by inhibition with free radical scavengers. The mechanism of ROS generation induced by V (V) involved the activation of an NADPH oxidase complex and the mitochondrial electron transport chain. The ROS scavenger, catalase (H(2)O(2) scavenger), effectively inhibited both lung cell apoptosis and the inflammatory response, whereas superoxide dismutase (SOD) (O(2)(*-) scavenger) and the metal chelator, deferoxamine (inhibitor of (*)OH generation by Fenton-like reactions) had lesser effects. These results indicate that multiple oxidative species are involved in V (V)-induced lung inflammation and apoptosis, and that H(2)O(2) plays a major role in this process.
authors.affiliation: Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA. lmw6@cdc.gov
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
authors.forename: Djordje
authors.initials: D
authors.lastname: Medan
authors.forename: Robert
authors.initials: R
authors.lastname: Mercer
authors.forename: Dean
authors.initials: D
authors.lastname: Overmiller
authors.forename: Stephen
authors.initials: S
authors.lastname: Leornard
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Min
authors.initials: M
authors.lastname: Ding
authors.forename: Chuanshu
authors.initials: C
authors.lastname: Huang
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019097:Spin Trapping; D014638:Vanadates / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014638:Vanadates