Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium

Our plain-English summary of Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium, by M. Ruotsalainen, J. Naarala, K.M. Savolainen (Toxicology Letters, 1995).

The study

• Authors: M. Ruotsalainen, J. Naarala, K.M. Savolainen
• Journal: Toxicology Letters
• Published: 1995;78(3):195-205
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The role of intra- and extracellular calcium in the activation of human polymorphonuclear leukocytes (PMNL) to produce reactive oxygen metabolites (ROM) were studied by using soluble, formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), or particulate stimuli, quartz or chrysotile. A calcium channel inhibitor, verapamil, attenuated only quartz-induced elevation of free intracellular calcium ([Ca2+]i) and ROM production. Likewise, ethyleneglycol-bis (aminoethyl ether) tetraacetic acid (EGTA) attenuated quartz-, chrysotile- and fMLP-induced elevation of [Ca2+]i and ROM production. It also inhibited PMA-induced ROM production. A calcium ionophore, A23187 amplified ROM production by all of these stimuli. These results suggest that both intra- and extra-cellular calcium are required for the full activation of respiratory burst by soluble and particulate stimuli in human PMNL.

In plain English

This was a laboratory study of human white blood cells called polymorphonuclear leukocytes (PMNL). The cells were isolated from the blood of healthy adult donors, supplied by the Finnish Red Cross. The authors exposed the cells to chrysotile asbestos (a UICC reference sample), quartz dust, or two chemical stimulants. They measured calcium inside the cells, and used light output (chemiluminescence, in mV) to gauge the cells' production of reactive oxygen metabolites. They then tested how three agents that block or boost calcium changed these responses. The calcium channel blocker verapamil reduced the quartz-induced calcium rise, by 64% at the highest dose, and reduced quartz-induced output by 35%. It did not reduce the chrysotile-induced calcium rise and had no significant effect on chrysotile-induced output. Removing calcium from outside the cells with EGTA cut the chrysotile-induced calcium rise by 56%, but only at the highest dose. It cut chrysotile-induced output by 96%. The calcium-boosting agent A23187 raised chrysotile-induced output from 40 to 231 mV. The authors concluded that calcium from outside the cells, as well as calcium released inside them, is required for full activation by mineral fibers.

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 human white blood cells isolated from donated blood
• Who was studied: Human polymorphonuclear leukocytes (PMNL) from venous blood of healthy adult donors who had taken no drugs for at least 7 days, supplied by the Finnish Red Cross. The number of donors is not stated. Each measurement was done 4 times in duplicate.
• Exposure: UICC reference Chrysotile A asbestos (250 µg/ml for calcium measurements, 200 µg/ml for reactive oxygen metabolite measurements) and Min-u-sil quartz dust, compared with the soluble stimulants fMLP and PMA. Cells were pre-treated with verapamil (1, 10, 100 µM), EGTA (0.5, 1.0, 5.0 mM) or A23187 (10, 100, 1000 nM).
• Main results:
  • Verapamil reduced the quartz-induced rise in intracellular calcium in a dose-dependent way, by 64% at the highest dose.
  • Verapamil did not reduce the chrysotile-induced rise in intracellular calcium.
  • In the verapamil experiments, quartz-induced chemiluminescence was 295 ± 22 mV and chrysotile-induced chemiluminescence was 17 ± 1 mV.
  • Verapamil at 100 µM decreased quartz-induced chemiluminescence to 191 ± 19 mV (a 35% decrease). It had no significant effect on chrysotile-induced chemiluminescence.
  • EGTA reduced the chrysotile-induced rise in intracellular calcium only at the highest dose (5.0 mM), from 68 ± 7 nM to 30 ± 8 nM (a 56% decrease).
  • EGTA decreased chrysotile-induced chemiluminescence in a dose-dependent way, from 51 ± 8 mV to 2 ± 0 mV (a 96% decrease).
  • A23187 at 100 nM increased quartz-induced chemiluminescence from 230 ± 8 mV to 508 ± 19 mV, and chrysotile-induced chemiluminescence from 40 ± 1 mV to 231 ± 14 mV.
  • A23187 did not change the rises in intracellular calcium caused by fMLP, PMA, quartz or chrysotile.
• The authors' conclusion: The authors concluded that influx of calcium from outside the cells, in addition to release of calcium stored inside them, is required for full activation of the reactive oxygen metabolite response stimulated by mineral fibers in human PMNL.

Topics

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

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Chrysotile.

Related studies

• 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)
• Production of reactive oxygen species by man-made vitreous fibres in human polymorphonuclear leukocytes — M. Ruotsalainen, M.R. Hirvonen, et al. (1999)
• Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by crocidolite asbestos — T. Ishizaki, E. Yano, et al. (1997)
• Asbestos-induced disruption of calcium homeostasis induces endoplasmic reticulum stress in macrophages — A.J. Ryan, J.L. Larson-Casey, et al. (2014)
• Crocidolite-induced reactive oxygen metabolites generation from human polymorphonuclear leukocytes — T. Ishizaki, E. Yano, et al. (1994)
• Role of extracellular calcium in chrysotile asbestos stimulation of alveolar macrophages — B. Kalla, R.F. Hamilton, et al. (1990)

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