Differential effects of mineral dusts on the in vitro activation of alveolar macrophage eicosanoid and cytokine release

Our plain-English summary of Differential effects of mineral dusts on the in vitro activation of alveolar macrophage eicosanoid and cytokine release, by K.E. Driscoll, J.M. Higgins, M.J. Leytart, et al (Toxicology in Vitro, 1990).

The study

• Authors: K.E. Driscoll, J.M. Higgins, M.J. Leytart, L.L. Crosby
• Journal: Toxicology in Vitro
• Published: 1990;4(4-5):284-8
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We investigated the in vitro effects of the pneumotoxic agents, silica and asbestos, and the relatively innocuous materials, aluminium oxide (Al(2)O(3)) and titanium dioxide (TiO(2)), on alveolar macrophages (AM) using endpoints reflecting the cytotoxic and AM activating properties of the dusts. Rat AM were exposed in vitro (24 hr) to 10-1000 mug/ml of the dusts. AM conditioned media was analysed for lactate dehydrogenase (cytotoxicity), beta-glucuronidase (lysosomal enzyme), leukotriene B4 (LTB4), prostaglandin E(2) (PGE(2)), tumour necrosis factor alpha (TNF) and interleukin-1 (IL-1). AM LTB4 and TNF release were increased by silica and asbestos but not by Al(2)O(3) or TiO(2). IL-1 release was not affected, and changes in PGE(2) release were minimal, after dust exposure. Cytotoxic activity was not consistently associated with LTB4, TNF or beta-glucuronidase release. The ability of silica and asbestos, but not Al(2)O(3) and TiO(2), to activate AM to release the pro-inflammatory mediators, LTB4 and TNF, may be responsible, at least in part, for the greater inflammation and pneumotoxicity associated with silica and asbestos exposure. These findings suggest that assessment of AM mediator secretion in vitro can provide information to understand better the potential of a material to cause respiratory toxicity.

In plain English

This was a laboratory study of rat lung cells, not of people. The authors collected alveolar macrophages (immune cells from the air sacs of the lungs) by washing out the lungs of male F344 rats. They exposed the cells in culture dishes for 24 hours to one of four dusts: silica, crocidolite asbestos, aluminium oxide or titanium dioxide. Concentrations were described as 10 to 1000 micrograms per millilitre. Results came from three experiments. Silica and crocidolite asbestos caused dose-related increases in the cells' release of two inflammation-promoting substances, leukotriene B4 and tumour necrosis factor (TNF). Aluminium oxide and titanium dioxide did not. Silica's effect on leukotriene B4 was stronger than that of asbestos. Asbestos did not increase release of lactate dehydrogenase, a marker of cell damage, but all silica doses did. None of the dusts stimulated interleukin-1. Prostaglandin E2 rose only slightly, at one silica dose. The authors concluded that the ability of silica and asbestos to trigger release of leukotriene B4 and TNF may be responsible, at least in part, for the lung inflammation and toxicity linked to inhaling them.

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: in vitro laboratory experiment on rat alveolar macrophages
• Who was studied: alveolar macrophages obtained by bronchoalveolar lavage from male SPF F344 rats; number of rats not stated; results from 3 experiments
• Exposure: 24-hour in vitro exposure to silica (minusil), crocidolite asbestos, aluminium oxide or titanium dioxide, stated as 10 to 1000 micrograms per millilitre; lipopolysaccharide used as a positive control in some experiments
• Main results:
  • Silica and asbestos (crocidolite) caused dose-related increases in macrophage leukotriene B4 production, with silica's effect more pronounced than asbestos's
  • Silica and asbestos caused a dose-related stimulation of TNF release by the macrophages
  • Aluminium oxide and titanium dioxide did not produce the TNF and leukotriene B4 response
  • Asbestos did not increase release of lactate dehydrogenase (the cell-damage marker)
  • All silica exposure levels increased lactate dehydrogenase release
  • All four dusts increased beta-glucuronidase release, with silica having the most pronounced effect
  • Prostaglandin E2 did not change after dust exposure, except for a slight rise at 100 micrograms per millilitre silica
  • None of the dusts stimulated interleukin-1 release
  • The dusts' cell-damaging activity did not consistently match their ability to stimulate leukotriene B4 or TNF release
• The authors' conclusion: The authors concluded that the ability of silica and asbestos to directly stimulate macrophage leukotriene B4 and TNF release may be responsible, at least in part, for the lung inflammation and toxicity associated with inhaling these materials

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Cytokine, Lactate Dehydrogenase (LDH), Necrosis, Inflammation, Asbestos Exposure.

Related studies

• Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release — G.D. Leikauf, S.P. Fink, et al. (1995)
• Distinctive profile of alveolar macrophage-derived cytokine release induced by fibrogenic and nonfibrogenic mineral dusts — I. Lemaire, S. Ouellet (1996)
• Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages — L.J. Geist, L.S. Powers, et al. (2000)
• Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure — R.C. Perkins, R.K. Scheule, et al. (1993)
• Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes — T.O. Khaliullin, E.R. Kisin, et al. (2020)
• Stimulation of alveolar macrophages by mineral dusts in vitro: luminol-dependent chemiluminescence study — V. Vilím, J. Wilhelm, et al. (1987)

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