Fibrogenesis

Our plain-English summary of Fibrogenesis, by J.S. Harington (Environmental Health Perspectives, 1974).

The study

• Author: J.S. Harington
• Journal: Environmental Health Perspectives
• Published: 1974;9:271-9
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A review of fibrogenesis by asbestos fibers is given. There is nothing to indicate that the fibrogenic effects of inhaled asbestos fibers should differ in any way from those of ingested asbestos. Recently, ingestion has assumed some importance concerning human exposure. Three sections dealing with the process of fibrogenesis are covered: the first deals with in vitro fibrogenesis, in particular the interrelation of macrophages damaged by dusts and the subsequent laying down of collagen by fibroblasts in culture; the second deals with in vivo fibrogenesis after the inoculation of extracts of silica-treated macrophages into various animals, and the third, with the fibrogenicity of a wide variety of mineral fibers in man and experimental animals. Recent studies described in the first section of the present review appear to offer a better understanding of the effects of macrophages on fibroblasts after tissue damage of various kinds has occurred.

In plain English

This was a review, by an author in Johannesburg, of how asbestos and other mineral dusts cause fibrosis, the laying down of collagen. It mainly described earlier studies but also mentioned unpublished results from the author's group. The author stated nothing indicated that inhaled and ingested asbestos differ in fibrogenic effects. The review covered macrophages and fibroblasts in culture, injection of silica-treated macrophage extracts into animals, and the fibrogenicity of mineral fibers in people and animals. Studies reviewed reported that chrysotile was the most toxic fiber type to macrophages. They also reported that all forms of asbestos, and glass and other non-asbestos fibers, could stimulate collagen production in animals. Cell-culture results with silica-treated macrophages conflicted. Some studies found stimulation, while the author's group found 60-80% inhibition of collagen production when silica-treated hamster macrophages were added to hamster fibroblasts. Another study linked the outcome to whether the fibroblasts were still dividing. In mice, long fibers injected into the pleural cavity produced more fibrous tissue than short ones. The author concluded that longer fibers are probably more effective than shorter ones in producing asbestosis in experimental animals.

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: narrative review of laboratory, animal and human studies on fibrogenesis (collagen formation) by asbestos and other dusts, including some unpublished results from the author's group
• Who was studied: no single study population; the review covered cell-culture studies of macrophages and fibroblasts from several animal species, injection studies in animals, and studies of mineral fiber fibrogenicity in man and experimental animals
• Exposure: ingested and inhaled asbestos fibers (chrysotile, amosite, crocidolite), forms of silica, glass fibers, man-made insulation fibers and other minerals; also extracts of livers poisoned with carbon tetrachloride
• Main results:
  • Recent studies reviewed found that chrysotile showed the greatest toxicity to macrophages of all fiber types, for both early and late cytotoxicity. Other forms showed generally weak toxic effects.
  • The author stated that death of the macrophage is a prerequisite to fibrogenesis, although the biochemical steps between the two had not been worked out.
  • The author stated that all forms of asbestos fibers can stimulate collagen production in experimental animals. Glass and other non-asbestos fibers can do so too, which the author said emphasizes the fibrous nature of the material over its chemical composition.
  • In a study by Harington et al., suspensions of silica-treated hamster macrophages added to hamster fibroblasts in culture caused a marked inhibition of collagen production (60-80%) over an 11-day period. Heppleston and Styles had earlier reported stimulation of collagen synthesis.
  • In unpublished results, Harington and Corfield found a complete shut-off of collagen synthesis when extracts of rat liver poisoned with carbon tetrachloride, or of normal rat liver, were added to hamster fibroblasts in culture.
  • Nourse et al. found that silica-treated macrophages inhibited collagen synthesis when the fibroblasts were no longer dividing. When the fibroblasts were still dividing, a factor was produced that increased collagen synthesis.
  • Davis injected a range of mineral dusts and fibers into the pleural cavity of mice. Long-fiber samples produced large granulomas that were eventually replaced by large amounts of fibrous tissue. Short-fiber or nonfibrous, finely ground dusts stimulated much less reaction.
  • Richards et al. exposed rabbit lung fibroblast cultures to Rhodesian chrysotile, glass fiber, coal and quartz. Chrysotile significantly increased the amount of collagen in the cell mat. The author said a direct effect of asbestos on fibroblasts, without macrophages, cannot yet be taken as established.
• The authors' conclusion: The author concluded that longer fibers are probably more effective than shorter ones in producing asbestosis in experimental animals. The author also stated that nothing indicates the fibrogenic effects of inhaled and ingested asbestos differ.
• Limitations the authors state:
  • The author noted that the biochemical steps between macrophage death and fibrogenesis had not yet been worked out.
  • The author noted inconsistencies in the results of studies injecting extracts of silica-treated macrophages into animals.
  • The author cautioned that collagen production in cell culture is complex and affected by many variables, such as the medium and the cells' growth rate.

Topics

Medical terms in this study, explained in our Lexicon: Fibrogenic, Macrophage, Collagen, Fibroblast, Mineral Fiber.

Related studies

• Pharmacology of fibrosis and tissue injury — M. Chvapil (1974)
• Fibrogenesis by mineral fibres: an in-vitro study of the roles of the macrophage and fibre length — M. Aalto, A.G. Heppleston (1984)
• Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia — K. Vuorinen, F. Gao, et al. (2007)
• Biochemical effects of asbestiform minerals on lung fibroblast cultures — P.M. Hext, R.J. Richards (1976)
• The long term fibrogenic effects of chrysotile and crocidolite asbestos dust injected into the pleural cavity of experimental animals — J.M. Davis (1970)
• Some biochemical effects of asbestos on macrophages — K. Miller, J.S. Harington (1972)

Browse more research in Environmental Health Perspectives, or return to medical research.