Role of extracellular calcium in chrysotile asbestos stimulation of alveolar macrophages

Our plain-English summary of Role of extracellular calcium in chrysotile asbestos stimulation of alveolar macrophages, by B. Kalla, R.F. Hamilton, R.K. Scheule, et al (Toxicology and Applied Pharmacology, 1990).

The study

• Authors: B. Kalla, R.F. Hamilton, R.K. Scheule, A. Holian
• Journal: Toxicology and Applied Pharmacology
• Published: 1990;104(1):130-8
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The purpose of these studies was to determine whether extracellular calcium and calcium channels can influence chrysotile asbestos-stimulated production of superoxide anion by guinea pig alveolar macrophages. Increasing the extracellular calcium concentration from 0.0 to 10.0 mM markedly enhanced the ability of noncytotoxic levels of chrysotile (25 micrograms/ml) to stimulate macrophage production of superoxide anion at 37 degrees C. The primary effect of increasing extracellular calcium was to prolong superoxide anion production. In parallel with these calcium-dependent effects on superoxide anion production, chrysotile also caused an elevation of cytosolic calcium (measured using Fura-2) which increased with increasing extracellular calcium concentrations. A number of organic calcium channel antagonists were tested for their ability to block chrysotile-stimulated superoxide anion production by cells in medium containing physiological levels of calcium. The relative order of potency of these antagonists was verapamil much greater than nimopidine approximately diltiazem approximately nifedipine greater than segontin. In parallel with its effects on superoxide anion production, verapamil also partially blocked the observed chrysotile-stimulated elevation of cytosolic calcium. Taken together, these results suggest that chrysotile can open calcium channels on the macrophage surface, allowing extracellular calcium to enter and contribute to the elevation of cytosolic calcium levels. This elevation of cytosolic calcium in turn serves to prolong chrysotile-stimulated superoxide anion production.

In plain English

This laboratory study used alveolar macrophages, a type of lung immune cell, taken from male Hartley guinea pigs. The authors exposed the cells to chrysotile asbestos at 25 micrograms per millilitre and measured superoxide anion, a reactive oxygen product. Chrysotile set off an early burst of superoxide lasting about 3 minutes, and this burst did not depend on calcium in the surrounding fluid. A later phase did depend on that calcium. At physiological calcium levels (1 to 2 mM), about two-thirds of the superoxide made in 10 minutes came from this later phase. Chrysotile also raised calcium inside the cells, with a larger and longer rise when more calcium was outside. Of five calcium channel blockers tested, only verapamil significantly reduced chrysotile-stimulated superoxide. Verapamil also blocked the part of the inside-cell calcium rise that came from outside calcium. The authors concluded that their results were consistent with verapamil-sensitive calcium channels being involved in chrysotile stimulation of macrophages. They suggested this might help explain chronic inflammation in asbestos-associated diseases.

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 animal cells
• Who was studied: Alveolar macrophages from male Hartley guinea pigs; each experiment was performed at least three times
• Exposure: Chrysotile asbestos (RG-144), fibers sized 1 to 5 micrometres, at 25 micrograms per millilitre. It was tested at extracellular calcium levels from 0.0 to 10.0 mM, with and without calcium channel blockers (verapamil, nifedipine, diltiazem, nimopidine, segontin).
• Main results:
  • The early phase of chrysotile-stimulated superoxide production (about the first 3 minutes) was essentially independent of extracellular calcium.
  • Total superoxide over 10 minutes rose with extracellular calcium and leveled off at about 0.5 mM. At physiological calcium (1 to 2 mM), about two-thirds came from the calcium-dependent late phase.
  • Of the five calcium channel antagonists tested, only verapamil significantly inhibited chrysotile-stimulated superoxide production over 1 hour, at 25 or 50 micromolar.
  • Verapamil at 50 micromolar had no significant effect on superoxide production stimulated by the soluble agonist FNLP; the data were not shown.
  • In 2 mM extracellular calcium, chrysotile caused a larger and sustained rise in calcium inside the cells, compared with the low-calcium medium.
  • Verapamil at 50 micromolar blocked the extracellular part of the chrysotile-stimulated rise in calcium inside the cells.
  • Over 1 hour at the chrysotile dose used, cell viability fell by 5 plus or minus 0.7% without added calcium and by 2.3 plus or minus 0.7% with 2 mM calcium. The authors considered this cytotoxicity minimal.
• The authors' conclusion: The authors concluded that their results were consistent with verapamil-sensitive calcium channels being involved in chrysotile stimulation of macrophages. They suggested that chrysotile's ability to prolong oxygen radical production may provide a mechanistic link to the chronic inflammation seen in asbestos-associated diseases.
• Limitations the authors state:
  • The authors did not follow superoxide production beyond the measured time periods. Their statement that the late phase accounts for most superoxide at longer times is an inference.
  • The authors noted that very little was known about the types of calcium channels present on macrophages.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Alveolar Macrophage, Superoxide, Macrophage.

Related studies

• Stimulation of alveolar macrophages by mineral dusts in vitro: luminol-dependent chemiluminescence study — V. Vilím, J. Wilhelm, et al. (1987)
• Rapid screening of possible cytotoxic effects of particulate air pollutants by measurement of changes in cytoplasmic free calcium, cytosolic pH, and plasma membrane potential in alveolar macrophages by flow cytometry — A. Tárnok, M. Dörger, et al. (2001)
• Activated alveolar macrophages express the insulin-like growth factor-I receptor — W.N. Rom, P. Pääkkö (1991)
• IgG specifically enhances chrysotile asbestos-stimulated superoxide anion production by the alveolar macrophage — R.K. Scheule, A. Holian (1989)
• Secretion of fibronectin by mineral dust-derived alveolar macrophages and activated peritoneal macrophages — R. Davies, G. Erdogdu (1989)
• Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium — M. Ruotsalainen, J. Naarala, et al. (1995)

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