Vanadium-induced apoptosis and pulmonary inflammation in mice: Role of reactive oxygen species

Liying Wang, Djordje Medan, Robert Mercer, Dean Overmiller, Stephen Leornard, Vincent Castranova, Xianglin Shi, Min Ding, Chuanshu Huang, Yon Rojanasakul

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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 O2-, H2O2, 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 (H2O2 scavenger), effectively inhibited both lung cell apoptosis and the inflammatory response, whereas superoxide dismutase (SOD) (O2- 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 H2O2 plays a major role in this process.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalJournal of Cellular Physiology
Volume195
Issue number1
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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