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

Environmental Research
T IshizakiP H Evans

Abstract

In our previous study, we demonstrated that reactive oxygen metabolites (ROM) generation from phagocytic cells may be involved in the carcinogenic mechanism of crocidolite asbestos. In the present study, the mechanism of human polymorphonuclear leukocytes (PMN) to generate ROM by crocidolite was investigated using verapamil, a calcium channel inhibitor; staurosporine, a NADPH oxidase inhibitor; and cytochalasin B (CB), an inhibitor of phagocytosis. The results indicate that whereas verapamil and staurosporine inhibited the crocidolite-induced ROM generation from PMN dose-dependently, CB caused an enhancement. We conclude that crocidolite-induced ROM generation involves a cell surface reaction due to influx of extracellular calcium through calcium channels and the activation of NADPH oxidase on the PMN cell membrane. This hypothesis was indirectly supported by dose-dependent enhancement of the ROM generation by CB, as CB increases calcium ion permeability in PMN. However, as in our previous studies, the time course of the ROM generation and the cell type difference suggested that ROM were also generated intracellularly from PMN due to phagocytosis of crocidolite. In conclusion, our evidence indicates that ROM generation from PMN...Continue Reading

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Feb 14, 2004·American Journal of Respiratory Cell and Molecular Biology·A Brent CarterGary W Hunninghake
Jun 22, 1999·Thorax·D W Kamp, S A Weitzman
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Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Haining YangMichele Carbone

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