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Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by

T Ishizaki1, E Yano, P H Evans

  • 1Department of Hygiene Public Health, Teikyo University School of Medicine, Tokyo, Japan.

Environmental Research
|January 7, 1998
PubMed

Insights

Crocidolite asbestos exposure triggers reactive oxygen metabolite (ROM) generation in human white blood cells (PMN) via cell surface reactions and intracellular processes. Inhibitors reveal calcium channels and NADPH oxidase involvement, while phagocytosis enhances ROM production.

Area of Science:

  • Toxicology
  • Cell Biology
  • Immunology

Background:

  • Previous research linked reactive oxygen metabolite (ROM) generation by phagocytic cells to crocidolite asbestos carcinogenicity.
  • The precise mechanisms by which crocidolite asbestos induces ROM generation in human polymorphonuclear leukocytes (PMN) remained to be fully elucidated.

Purpose of the Study:

  • To investigate the specific cellular mechanisms underlying crocidolite asbestos-induced ROM generation in human PMN.
  • To determine the roles of calcium influx, NADPH oxidase activity, and phagocytosis in this process.

Main Methods:

  • Human PMN were exposed to crocidolite asbestos in the presence of inhibitors: verapamil (calcium channel inhibitor), staurosporine (NADPH oxidase inhibitor), and cytochalasin B (CB, phagocytosis inhibitor).
  • ROM generation was measured to assess the impact of each inhibitor on the cellular response.

Main Results:

  • Verapamil and staurosporine significantly inhibited crocidolite-induced ROM generation in a dose-dependent manner.
  • Cytochalasin B enhanced ROM generation, suggesting a role for increased calcium permeability.
  • Time course and cell type differences indicated both cell surface and intracellular (phagocytosis-dependent) ROM generation.

Conclusions:

  • Crocidolite-induced ROM generation in PMN involves direct cell surface interactions mediated by extracellular calcium influx through calcium channels and subsequent NADPH oxidase activation.
  • Phagocytosis of crocidolite also contributes to intracellular ROM generation.
  • The dual mechanism highlights the complex cellular response to asbestos exposure.

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