Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis

Our plain-English summary of Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis, by K. Donaldson, G.M. Brown, D.M. Brown, et al (The Journal of Pathology, 1990).

The study

• Authors: K. Donaldson, G.M. Brown, D.M. Brown, J. Slight, M.D. Robertson, J.M. Davis
• Journal: The Journal of Pathology
• Published: 1990;160(1):63-9
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Rats were exposed to clouds of the following pneumoconiotic dusts: quartz, coal-mine dust, and chrysotile asbestos at 10 or 50 mg/m3 for 8, 32, and 75 days; for comparison, rats were also exposed to the non-pathogenic dust titanium dioxide (TiO2). The bronchoalveolar leukocytes (macrophages and neutrophils) from dust-exposed and control rats were obtained by lavage and tested for their ability to migrate toward zymosan-activated serum. Varying amounts of neutrophils were present depending on the ability of the dust to cause inflammation and the length of exposure. There was a marked loss of chemotactic ability in leukocytes from rats inhaling the pneumoconiotic dusts compared with controls; TiO2-exposed leukocytes had some impairment of chemotaxis, but this was substantially less than that found with the pneumoconiotic dusts. The loss of chemotactic activity did not correlate with the percentage of neutrophils in the lavage cells except when there were very high levels of neutrophils, and there was substantial impairment of chemotaxis with negligible numbers of neutrophils, showing that macrophage chemotaxis was impaired. A phagocytic burden within the leucocytes was not sufficient alone to inhibit chemotaxis, nor was the loss of chemotactic activity due to occupied receptors, since incubation failed to restore chemotaxis. Loss to chemotactic activity by leukocytes from pneumoconiotic dust-exposed lung could be an important factor in the development of pneumoconiosis.

In plain English

This animal experiment tested whether lung white blood cells lose their ability to move toward a chemical signal (chemotaxis) after rats breathe dusts that cause pneumoconiosis. Rats inhaled quartz, coal-mine dust, chrysotile asbestos, or titanium dioxide, which the authors called a non-pathogenic dust. Exposure was 10 mg/m3 (coal-mine dusts also 50 mg/m3) for 8, 32 or 75 days. Cells washed from the lungs were tested in chambers. Cells from rats breathing quartz, coal-mine dust and chrysotile showed a marked loss of chemotaxis compared with controls. Titanium dioxide caused 25 per cent inhibition at 8 days and no more than 17 per cent afterward. Chrysotile quickly caused lung inflammation. Chrysotile and quartz caused significantly more inhibition than titanium dioxide at 8 days. The loss occurred in macrophages even when few neutrophils were present. Dust taken up by normal macrophages in the laboratory did not impair their chemotaxis. Separately, 4 hours of incubation did not restore movement in impaired cells from rats given coal-mine dust for 75 days. The authors concluded the effect appears relevant to how pneumoconiosis develops.

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: Animal experiment (inhalation exposure of rats, with an additional intratracheal instillation experiment and laboratory cell experiments)
• Who was studied: Syngeneic PVG rats, 15 weeks old at the start of exposure. They were exposed in groups of 48. At each time-point, lavage cells from four dust-exposed rats and two room-air control rats were pooled for testing.
• Exposure: Inhaled dust clouds of quartz (standard DQ12), coal-mine dust from British collieries mining anthracite (A), high rank coal (H) and low rank coal (L), chrysotile asbestos (UICC standard sample), and titanium dioxide (rutile) for comparison. Exposure was at target airborne mass concentrations of 10 or 50 mg/m3 (50 mg/m3 for coal-mine dusts) for 8, 32 or 75 days. In a separate experiment, 1 mg of quartz was instilled into the trachea.
• Main results:
  • Leukocytes from rats inhaling quartz, coal-mine dust and chrysotile asbestos showed a marked loss of chemotactic ability compared with controls.
  • At 10 mg/m3, chrysotile rapidly caused an inflammatory response in the lungs, whereas the other pneumoconiotic dusts showed little effect initially.
  • In rats exposed to titanium dioxide, chemotaxis was inhibited by 25 per cent at 8 days and by no more than 17 per cent thereafter.
  • Compared with titanium dioxide, inhibition was significantly greater (P less than 0.05) with quartz and chrysotile at 8 days, and with all pneumoconiotic dusts at 32 and 75 days.
  • For all three coal-mine dusts, inhibition of chemotaxis was significantly greater at 50 mg/m3 than at 10 mg/m3.
  • Quartz instilled into the trachea also significantly reduced chemotaxis of the lung leukocytes.
  • Loss of chemotaxis was present in macrophages, shown by substantial loss when neutrophil levels were negligible.
  • Normal (control) macrophages that took up quartz, titanium dioxide or chrysotile in the laboratory for 1 hour were not impaired in chemotaxis.
  • In a separate experiment, incubating cells with already-impaired chemotaxis, obtained from rats exposed to coal-mine dust for 75 days, for 4 hours did not restore their chemotaxis.
• The authors' conclusion: The authors concluded that finding impaired chemotaxis with three different pneumoconiotic dusts, but not with titanium dioxide, suggests the phenomenon is relevant to the development of pneumoconiosis.
• Limitations the authors state:
  • Only limited experiments were done to investigate the mechanism of the loss of chemotaxis.
  • When neutrophils were present in high proportions, their weaker migration may have influenced the assay result.
  • Whether the loss reflects an effect on cell movement or a loss of receptors was not determined and was left for future study.

Topics

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

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Chrysotile, Macrophage, Inflammation.

Related studies

• Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide — K. Donaldson, R.E. Bolton, et al. (1988)
• The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro — K. Donaldson, J. Slight, et al. (1988)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)
• Accumulation of mixed mineral dusts in the lungs of rats during chronic inhalation exposure — C.H. McMillan, A.D. Jones, et al. (1989)
• The chemiluminescent response of human phagocytic cells to mineral dusts — I.P. Gormley, M.J. Kowolik, et al. (1985)
• Experimental infective pneumoconiosis: effect of asbestos dust and Candida albicans infection on the lungs of rhesus monkeys — S.H. Zaidi, R. Shanker, et al. (1973)

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