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

Our plain-English summary of Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by crocidolite asbestos, by T. Ishizaki, E. Yano, P.H. Evans (Environmental Research, 1997).

The study

• Authors: T. Ishizaki, E. Yano, P.H. Evans
• Journal: Environmental Research
• Published: 1997;75(2):135-40
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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 by crocidolite involves cellular mechanisms related both to direct cell surface membrane interactions, together with an apparent phagocytic-dependent process.

In plain English

This was a laboratory experiment on human white blood cells called polymorphonuclear leukocytes (PMN), isolated from human blood. The number of donors was not reported. The researchers exposed the cells to a standard (UICC) sample of crocidolite asbestos and measured reactive oxygen metabolites as light given off over 20 minutes. Before exposure, some cells were treated with verapamil (a calcium channel blocker), staurosporine (an enzyme inhibitor) or cytochalasin B (which blocks the cells' uptake of particles). Verapamil and staurosporine each reduced the response to crocidolite in a dose-dependent way. Cytochalasin B increased the response to crocidolite. With zymosan, a comparison particle, it reduced the response instead. The authors concluded that crocidolite may trigger these molecules at the cell surface, through calcium entering the cells and activation of NADPH oxidase. Citing their earlier study, they suggested that the cells also produce the molecules internally after engulfing crocidolite. They noted that cell viability declined over time, so absolute values varied. The figures shown are typical examples of experiments run in triplicate.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment on isolated human cells, comparing treated and untreated cells in parallel, in triplicate
• Who was studied: Polymorphonuclear leukocytes (PMN) isolated from human blood. The number of donors is not stated.
• Exposure: UICC standard crocidolite asbestos, compared with zymosan (a particle) and FMLP (a soluble activator). Cells were pretreated with cytochalasin B (125 and 500 ng/ml), verapamil (four concentrations) or staurosporine (12.5, 25 and 50 nM).
• Main results:
  • In PMN pretreated with cytochalasin B, the light-signal response (chemiluminescence) to crocidolite or FMLP increased dose-dependently. The response to zymosan decreased dose-dependently.
  • Verapamil pretreatment inhibited the crocidolite-induced response in a dose-dependent way.
  • Staurosporine inhibited the chemiluminescence induced by FMLP or crocidolite in a dose-dependent way.
  • Staurosporine had no effect on the zymosan-induced chemiluminescence (data not shown).
  • Zymosan produced a smaller response than FMLP but a greater response than crocidolite.
• The authors' conclusion: The authors concluded that crocidolite-induced reactive oxygen metabolite generation from PMN may come from a cell surface reaction involving calcium influx and NADPH oxidase activation. Based on their previous study, they also suggested that the metabolites are generated inside the cells after phagocytosis of crocidolite.
• Limitations the authors state:
  • PMN viability declined after the cells were prepared, so absolute chemiluminescence values varied depending on timing.
  • The figures shown are typical examples from single experiments rather than pooled data.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Carcinogenic, Phagocytosis.

Related studies

• Crocidolite-induced reactive oxygen metabolites generation from human polymorphonuclear leukocytes — T. Ishizaki, E. Yano, et al. (1994)
• Chemiluminescent detection of induced reactive oxygen metabolite production of human polymorphonuclear leucocytes by anthophyllite asbestos — T. Iwata, N. Kohyama, et al. (2002)
• Production of reactive oxygen metabolites induced by asbestos fibres in human polymorphonuclear leucocytes — M. Hedenborg, M. Klockars (1987)
• Production of reactive oxygen species by man-made vitreous fibres in human polymorphonuclear leukocytes — M. Ruotsalainen, M.R. Hirvonen, et al. (1999)
• Changes in free intracellular calcium and production of reactive oxygen metabolites in human leukocytes by soluble and particulate stimuli — M. Tuomala, M.R. Hirvonen, et al. (1993)
• IgG and IgA enhance the chrysotile-induced production of reactive oxygen metabolites by human polymorphonuclear leucocytes — M. Klockars, M. Hedenborg, et al. (1989)

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