The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro

Our plain-English summary of The ability of inflammatory bronchoalveolar leucocyte populations elicited with microbes or mineral dust to injure alveolar epithelial cells and degrade extracellular matrix in vitro, by K. Donaldson, J. Slight, G.M. Brown, et al (British Journal of Experimental Pathology, 1988).

The study

• Authors: K. Donaldson, J. Slight, G.M. Brown, R.E. Bolton
• Journal: British Journal of Experimental Pathology
• Published: 1988;69(3):327-38
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Inflammatory cells are recruited to the parenchyma of the lung in a range of conditions where they are considered to have the ability to exert damaging effects on elements of the alveolus. The injurious effects of rat bronchoalveolar-derived inflammatory cells on an alveolar Type II epithelial cell line were therefore assessed. Inflammatory populations produced by intratracheal injection of Corynebacterium parvum or quartz caused non-lethal detachment injury to the epithelial cells on co-culture whereas control bronchoalveolar cells had no effect on epithelial cells. The pathogenic mineral dusts quartz and chrysotile asbestos caused increased detachment injury when added to co-cultures of epithelial cells and bronchoalveolar leucocyte populations; neither titanium dioxide, a control mineral dust, nor zymosan were active in this respect. Detachment injury was particularly marked when quartz was added to co-cultures of epithelial cells and inflammatory bronchoalveolar cells from quartz treated lung. On the basis of anti-protease and anti-oxidant studies, the detachment injury was found to be mediated by protease alone in the case of quartz cells and protease plus oxidant in the case of C. parvum cells. The two inflammatory bronchoalveolar cell populations were found to have increased proteolytic activity, compared to control bronchoalveolar cells, as shown by increased ability to degrade fibronectin, laminin and denatured collagen. Inflammatory bronchoalveolar cells therefore have the potential to attack elements of the septal extracellular matrix as well as to compromise the integrity of the alveolar epithelium.

In plain English

This was a laboratory study in rats and cultured cells. The authors injected heat-killed Corynebacterium parvum bacteria or quartz into rats' windpipes to cause lung inflammation. They washed cells out of the lungs and placed them on A549 cells, human lung tumour cells resembling alveolar Type II cells. Cells from inflamed lungs made the epithelial cells detach without killing them; cells from untreated rats did not. UICC chrysotile asbestos 'A' and quartz, added directly to the dishes, increased detachment, with statistically significant increases at some concentrations. The authors called this effect modest, except when quartz was added to cells from quartz-treated lungs. Titanium dioxide and zymosan did not trigger substantial injury. Inhibitor tests pointed to protein-digesting enzymes (proteases) for cells from quartz-treated lungs, and to proteases plus oxidants for cells from C. parvum-treated lungs. Both inflammatory cell groups broke down fibronectin, laminin and denatured collagen more than control cells. No rats were given asbestos. The authors noted that human lung inflammation is likely considerably less intense than in their experiment, except possibly in adult respiratory distress syndrome (ARDS).

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 and in vitro laboratory experiment: lung-lavage cells from rats co-cultured with an alveolar epithelial cell line
• Who was studied: SPF, syngeneic PVG rats aged 10 weeks or older from the Institute of Occupational Medicine Animal Unit (cell composition based on five rats per group), plus A549 cells, a Type II-like cell line from a human lung tumour. Dates are not given.
• Exposure: Rats were injected into the trachea with 1.4 mg heat-killed Corynebacterium parvum or 1 mg DQ12 quartz. In the dishes, titanium dioxide (rutile), UICC chrysotile asbestos 'A', DQ12 quartz, zymosan and PMA were added as triggers at concentrations including 10 and 100 micrograms per ml. Chrysotile was used only in the dishes, not injected into rats.
• Main results:
  • Lung-lavage cells from C. parvum-treated rats were 89.8 plus or minus 6.7% neutrophils, and from quartz-treated rats 45.0 plus or minus 6.7% neutrophils. Control cells had 0% neutrophils.
  • Cells from both groups of inflamed lungs caused detachment of epithelial cells (P less than 0.001); control lung cells did not. No group of lung cells killed (lysed) the epithelial cells.
  • With control lung cells, chrysotile and quartz at 100 micrograms per ml significantly increased detachment (P less than 0.001)
  • With cells from C. parvum-treated lungs, quartz and chrysotile asbestos at 10 micrograms per ml, and PMA, significantly increased detachment (P less than 0.001)
  • With cells from quartz-treated lungs, quartz at 10 and 100 micrograms per ml, chrysotile at 100 micrograms per ml, and PMA significantly increased detachment (P less than 0.001)
  • The authors described the dust effects as modest, except for quartz added to cells from quartz-treated lungs, which produced large increases in detachment
  • Titanium dioxide and zymosan did not trigger substantial detachment injury
  • Based on inhibitor tests, detachment was attributed to protease alone for cells from quartz-treated lungs, and to protease plus oxidant for cells from C. parvum-treated lungs
  • Breakdown of fibronectin, measured in counts per minute, was 4382 plus or minus 601 for cells from C. parvum-treated lungs versus 2105 plus or minus 183 for control cells. In a separate experiment it was 2124 plus or minus 93 for cells from quartz-treated lungs versus 935 plus or minus 216 for control cells. Both differences were significant (P less than 0.001), and similar increases were seen for laminin and denatured collagen.
  • Albumin in lavage fluid, a sign of leaky lungs, was 1.5 plus or minus 0.2 mg in quartz-treated rats and 2.6 plus or minus 0.3 mg in C. parvum-treated rats, versus about 0.4 mg in controls. Both treated groups differed significantly from controls (P less than 0.001).
• The authors' conclusion: The authors concluded that inflammatory leucocytes that build up in lungs inflamed by mineral dust or microorganisms can injure alveolar epithelial cells and degrade extracellular matrix. They suggested these effects may be important in long-term remodelling or destruction of lung tissue.
• Limitations the authors state:
  • Alveolar inflammation in humans is likely considerably less intense than the inflammation produced in this experiment, except possibly in adult respiratory distress syndrome (ARDS)
  • In the lung, anti-protease and anti-oxidant defences may reduce the potential for injury
  • Macrophages and neutrophils were not separated, so the role of each cell type was not determined

Topics

Medical terms in this study, explained in our Lexicon: Parenchyma, Chrysotile, Collagen, Epithelium.

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)
• Asbestos fibre length-dependent detachment injury to alveolar epithelial cells in vitro: role of a fibronectin-binding receptor — K. Donaldson, B.G. Miller, et al. (1993)
• Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro — R.M. Jagirdar, E.D. Papazoglou, et al. (2021)
• The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• Progressive lung cell reactions and extracellular matrix production after a brief exposure to asbestos — L.Y. Chang, L.H. Overby, et al. (1988)
• Fibrinolysis by rat mesothelial cells in vitro: the effect of mineral dusts at non-toxic doses — K. Donaldson, G.M. Brown, et al. (1988)

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