Collagen synthesis and degradation during the development of asbestos-induced pulmonary fibrosis

Our plain-English summary of Collagen synthesis and degradation during the development of asbestos-induced pulmonary fibrosis, by M.G. Arden, I.Y. Adamson (Experimental Lung Research, 1992).

The study

• Authors: M.G. Arden, I.Y. Adamson
• Journal: Experimental Lung Research
• Published: 1992;18(1):9-20
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although pulmonary fibrosis results from exposure to a high level of asbestos, the relative contributions of increased synthesis and/or reduced degradation of total collagen and of any specific type of collagen are not clear. To examine collagen turnover, rats were instilled with crocidolite fibers via the trachea and killed at 1, 2, 4, 6, and 8 weeks. The left lobe was used to determine collagen synthesis by incubating lung pieces with [3H]proline and subsequently measuring 3-hydroxyproline (HYP). Collagenolytic activity was estimated from the release of soluble HYP after incubation of lung homogenates for 48 h. Ratios of collagen types I and III were assayed by gel electrophoresis, both on whole lung and on the labeled homogenate. As fibrosis develops, both total HYP and HYP per dry weight increase at 2 weeks and continue to rise over the experimental period with no differences in the ratio of total types I:III collagens. However, newly synthesized collagen showed an increase in type III at 2 weeks and later a higher proportion of type I collagen when compared with the control. Total collagenolytic activity of asbestos-treated lungs was the same as controls when expressed per dry weight, but was reduced when calculated per unit of collagen. However, active collagenolytic activity was lower than control values when expressed by HYP content and per dry weight at all times after asbestos. The results suggest that reduced degradation of collagen contributes to the fibrotic process in addition to the progressive increase in collagen synthesis, particularly the type I form.

In plain English

This was an animal experiment in rats. The authors put 0.5 mg of crocidolite asbestos in water into the lungs of Sprague Dawley rats and killed groups of four at 1, 2, 4, 6 and 8 weeks. Control rats received water only. The authors measured lung collagen (the main scar-tissue protein), new collagen production, the balance of collagen types I and III, and collagen breakdown. In asbestos-treated rats, total lung collagen was significantly higher than normal after 1 week and kept rising. Measured per milligram of dry lung, new collagen production in treated lungs was 2 to 3 times the control level from week 2 to week 8. New collagen leaned toward type III in the first 4 weeks and toward type I by 8 weeks, but the type I to III ratio in total lung collagen did not change significantly. Collagen-breaking activity from active enzymes was reduced from after 1 week through 8 weeks. The authors concluded that reduced collagen breakdown might occur alongside increased production as fibrosis develops. They noted that the breakdown rate itself was not measured.

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: sequential study in rats given asbestos into the lungs, compared with water-treated controls
• Who was studied: 150-g Sprague Dawley rats. Groups of four treated animals were killed at 1, 2, 4, 6 and 8 weeks. Control animals received water and were killed at zero time and at 8 weeks (number of controls not stated). Authors were at the Department of Pathology, University of Manitoba, Winnipeg, Canada.
• Exposure: Crocidolite asbestos of mixed fiber length, 0.5 mg in 0.5 mL sterile water, instilled into the lungs under mild anesthesia
• Main results:
  • In asbestos-treated rats, the number of alveolar macrophages recovered by lung lavage more than doubled by 1 week and stayed significantly above control values for 8 weeks
  • Total hydroxyproline (a measure of collagen) in the right lobe of asbestos-treated rats was significantly higher than normal after 1 week and increased progressively thereafter
  • In total lung collagen, the ratio of type I to type III collagen was not significantly changed from normal at any time studied
  • In asbestos-treated lungs, incorporation of labelled proline into hydroxyproline (new collagen synthesis), normalized per milligram dry weight, was 2 to 3 times the control level between 2 and 8 weeks after asbestos. Values at 2 weeks and later were significantly greater than control (P less than .01).
  • In newly synthesized cross-linked collagen, the ratio of type III to type I was higher in treated lungs than in controls for the first 4 weeks (P less than .05 at weeks 1, 2 and 4). It then fell significantly below normal as type I synthesis predominated (P less than .01 at weeks 6 and 8).
  • Total collagen-breaking (collagenolytic) activity, expressed per milligram of tissue hydroxyproline, was reduced beginning 2 weeks after asbestos. The authors report it did not change when expressed per dry weight.
  • Active (endogenous) collagenolytic activity was significantly reduced per milligram hydroxyproline and per dry weight from after 1 week, and stayed low up to 8 weeks
  • Attempts to measure collagenase activity directly in tissue extracts, lavage fluid or lavage cells were not successful; values stayed in the range of blanks or controls
• The authors' conclusion: The authors concluded that reduced collagen degradation might occur in the living lung during development of asbestos-induced fibrosis, in addition to increased collagen synthesis. They also concluded that collagen-lysing activity was not sufficient to keep up with the increased synthesis.
• Limitations the authors state:
  • The rate of collagen degradation was not measured directly. Collagenolytic activity was estimated from hydroxyproline released from lung homogenates.
  • The collagenase assay might not detect small changes in fibroblast metabolism. Collagenase released into lung tissue may bind to collagen fibers and be unavailable for assay.
  • Changes in collagen type ratio may not have been detectable in total lung collagen because of the large pool of unchanged existing collagen

Topics

Medical terms in this study, explained in our Lexicon: Collagen, Pulmonary Fibrosis, Crocidolite, Fibrosis.

Related studies

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• Degradation of cartilage proteoglycan and collagen by synovial cells. Stimulation by macrophages under activation by phagocytosis, lymphocyte factors, bacterial products or other inflammatory stimuli — C. Peeters-Joris, G. Vaes (1984)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Changes in autacoid and neuropeptide contents of lung cells in asbestos-induced pulmonary fibrosis — R. Day, S. Lemaire, et al. (1987)

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