Fibrogenesis by mineral fibres: an in-vitro study of the roles of the macrophage and fibre length

Our plain-English summary of Fibrogenesis by mineral fibres: an in-vitro study of the roles of the macrophage and fibre length, by M. Aalto, A.G. Heppleston (British Journal of Experimental Pathology, 1984).

The study

• Authors: M. Aalto, A.G. Heppleston
• Journal: British Journal of Experimental Pathology
• Published: 1984;65(1):91-9
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Evidence on the mechanism by which inhaled mineral fibres lead to pulmonary fibrosis has not been forthcoming. As with silica, a biphasic cell culture system was required to distinguish phagocytosis from collagen formation. Synthesis of total protein and collagen by rat fibroblasts was estimated by incorporation of labelled proline after treatment with the medium from rat peritoneal macrophages that had been cultured in the presence of different types of mineral fibre. The influence of fibre length was also examined. All the main varieties of asbestos reacted with macrophages to produce or release a fibrogenic factor. However, chrysotile and the longer amosite fibres evoked the response only after prolonging the period of incubation with macrophages, presumably by permitting more complete phagocytosis of curled or longer fibres. Short amosite fibres proved to be more active than longer ones and under certain conditions were as potent as quartz. Fibrous glass also possessed stimulatory properties and again a sample having a short length gave a stronger response than a long one. Collagen formation by asbestos thus appears to be mediated by a macrophage factor, so operating in a manner similar to that previously demonstrated for quartz. The conventional view that short fibres are comparatively insignificant in asbestos fibrogenesis cannot, on the present evidence, be sustained. Furthermore, it should not be assumed than man-made mineral fibres of respirable diameter are innocuous or that short ones can be ignored.

In plain English

This laboratory study used rat cells in culture to examine how mineral fibres might lead to lung scarring (fibrosis). Rat peritoneal macrophages, a type of scavenger cell, were exposed to UICC amosite, crocidolite, chrysotile B, tremolite, short and longer amosite fractions, and short and long glass fibres, with quartz as a standard. The culture medium from these cells was then given to rat fibroblasts, and their output of total protein and collagen was measured. When macrophages were incubated with particles for the longer period, total protein rose significantly with quartz and all asbestos samples, notably short amosite. Collagen rose with quartz, short amosite and UICC amosite. In a later series, every material tested (quartz, tremolite and both glass fibres) stimulated protein and collagen, and short glass fibres were more actively fibrogenic than long ones. Titanium dioxide had no effect. Chrysotile B and amosite applied directly to fibroblasts, without macrophages, did not stimulate protein synthesis. The authors concluded that short fibres, including short glass fibres, can generate the macrophage fibrogenic factor and that the emphasis on long fibres needs to be relaxed. They noted that the number of fibres each cell took up was unknown.

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 (cell culture). Medium from fibre-exposed macrophages was transferred to fibroblasts, and collagen formation was measured by labelled proline incorporation into hydroxyproline.
• Who was studied: Rat peritoneal macrophages exposed to particles, and rat fibroblasts (from subcutaneous sponge granulomas) treated with the macrophage medium. No human subjects.
• Exposure: UICC amosite, crocidolite and chrysotile B, plus tremolite; short and longer amosite fractions; short (JM100) and long (JM110) Johns-Manville glass fibres. Dorentrup quartz was the standard stimulant and titanium dioxide was also tested. The most effective fibre dose was 200 micrograms per ml of medium.
• Main results:
  • Fibre lengths: in the longer amosite fraction, 31% of fibres were longer than 5 micrometres and 17% longer than 10 micrometres. In the short fraction, only 0.5% were longer than 5 micrometres.
  • Series 1 (48-hour macrophage medium, preliminary): macrophage fibrogenic factor activity was provoked by quartz, amosite and crocidolite (and probably short amosite). Crocidolite gave a higher value than quartz, while chrysotile led to a small depression.
  • Series 2 (96-hour medium): total protein synthesis rose significantly with quartz and all asbestos samples, notably short amosite.
  • Series 2 (96-hour medium): collagen synthesis increased, with the highest significance for quartz and lesser degrees for short amosite and UICC amosite.
  • Series 3 (acetone-washed fibres, 48-hour medium): quartz and short amosite greatly stimulated total protein synthesis, and collagen synthesis also increased to a highly significant degree.
  • Series 3: collagen formation was depressed by longer amosite, and significantly by UICC amosite.
  • Series 4 (glass fibres and tremolite, 48-hour medium): total protein rose significantly with all materials, with short and long glass fibres close or equivalent to quartz.
  • Series 4: only quartz stimulated collagen formation.
  • Series 5 (96-hour medium): all materials (quartz, tremolite, short and long glass fibres) significantly stimulated both total protein and collagen synthesis.
  • Series 5: short glass fibres were more actively fibrogenic than long glass fibres. Short glass fibres and tremolite produced collagen levels exceeding those from quartz.
  • Titanium dioxide did not affect total protein or collagen synthesis.
  • Chrysotile B and amosite applied directly to fibroblasts, without macrophages, did not stimulate protein synthesis.
• The authors' conclusion: The authors concluded that short fibres, including short glass fibres in sufficient quantity, can generate the macrophage fibrogenic factor, and that the emphasis on long fibres needs to be relaxed.
• Limitations the authors state:
  • The number of fibres taken up by individual cells, and therefore the size of the stimulus each received, was unknown.
  • The first series was preliminary, and its replicate analyses were too few for statistical assessment.
  • Undetermined conditions in the experimental procedures may influence how much of the protein synthesis goes into collagen.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Pulmonary Fibrosis, Biphasic Mesothelioma, Phagocytosis, Collagen, Fibroblast, Fibrogenic, Chrysotile.

Related studies

• Effect of SiO2-liberated macrophage factor on protein synthesis in connective tissue in vitro — M. Aalto, H. Turakainen, et al. (1979)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization — K. Donaldson, X.Y. Li, et al. (1992)
• Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia — K. Vuorinen, F. Gao, et al. (2007)
• Macrophage functions after exposure to mineral fibers — F. Tilkes, E.G. Beck (1983)
• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)

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