Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages

Our plain-English summary of Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages, by I.Y. Adamson, D.H. Bowden (The American Journal of Pathology, 1990).

The study

• Authors: I.Y. Adamson, D.H. Bowden
• Journal: The American Journal of Pathology
• Published: 1990;137(3):523-9
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

The role of alveolar macrophage (AM)-derived secretory products in fibroblast stimulation after the instillation of long and short asbestos to rat lungs is now investigated. A pure sample of 1 mg long crocidolite (greater than 2.5 mu) induced pulmonary fibrosis in 8 weeks, but secretions of lavaged AM from these lungs did not enhance growth or collagen synthesis in cultured rat lung fibroblasts. In contrast, the same dose of short fibers did not produce pulmonary fibrosis, although AM lavaged from these lungs were increased in number, had more phagocytized fibers, and when incubated, secreted factors that stimulated fibroblasts in culture. When normal AM were exposed to these fiber samples for 24 hours in vitro, greater phagocytosis of particles occurred and each asbestos fiber sample induced secretion of an AM-derived growth factor for cultured fibroblasts. The results indicate that both long and short fibers are capable of inducing AM to secrete fibrogenic factors in vitro, but in vivo, cytokine secretion by AM into the alveolar spaces in response to short fibers is not associated with stimulation of the interstitial fibroblast. In contrast, pulmonary fibrosis after long fiber administration appears unrelated to an AM secretion and is probably caused by fiber penetration into the peribronchiolar tissue, where interstitial macrophage activation may occur over several weeks.

In plain English

This rat study asked whether alveolar macrophage secretions (scavenger cells in the lung's air spaces) explain why long, but not short, crocidolite fibers cause lung fibrosis. UICC crocidolite was separated into long fibers (mean 24.4 microns) and short fibers (over 98% shorter than 2.5 microns). The authors injected 1 mg of either into the windpipes of male Sprague Dawley rats; controls received water. After 8 weeks, only long-fiber rats had raised lung collagen and peribronchiolar granulomas. Washing short-fiber rats' lungs recovered many more alveolar macrophages; about 15% of these contained fibers, versus about 5% after long fibers. Fluid from these macrophages significantly stimulated growth and collagen production in cultured lung fibroblasts; fluid from long-fiber macrophages did not. In dishes, fluid from normal macrophages given the lower dose of either fiber did not change fibroblast DNA synthesis. At the higher dose, fluid from short-fiber macrophages significantly increased fibroblast growth and raised collagen production about 30%. Long fibers gave a much smaller significant growth increase, only with 0.5 ml of fluid. The authors concluded that long-fiber fibrosis is more likely related to macrophages within lung tissue than to alveolar macrophages.

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 (rats), with asbestos instilled into the lungs (in vivo) and normal lung macrophages exposed to asbestos in culture (in vitro)
• Who was studied: Male Sprague Dawley rats (250 g). For the in vivo part there were 10 rats per group (long fiber, short fiber, control), with 3 additional rats for lung sections. Macrophages lavaged from 10 normal rats were used for the in vitro part. The study was done at the University of Manitoba, Winnipeg, Canada; the study dates are not given.
• Exposure: Standard UICC crocidolite asbestos was separated by sedimentation into long fibers (mean 24.4 microns, 88% longer than 2.5 microns) and short fibers (mean 0.6 microns, more than 98% shorter than 2.5 microns). In vivo, 1 mg of either was injected intratracheally in 0.5 ml sterile water, and the rats were killed 8 weeks later. In vitro, normal macrophages were incubated with 10 or 100 micrograms per ml of short, long, or no asbestos.
• Main results:
  • At 8 weeks, lung hydroxyproline (a measure of collagen and fibrosis) was significantly higher than controls only in the long-fiber rats. The short-fiber rats showed no change.
  • Lungs of long-fiber rats showed peribronchiolar interstitial granulomas at 8 weeks. After short fibers, the lung structure was normal.
  • Many more alveolar macrophages were recovered by lavage from the short-fiber group. After long fibers, the difference from controls was not significant.
  • At 8 weeks, about 15% of lavaged macrophages from short-fiber rats contained asbestos, compared with about 5% of lavaged cells from long-fiber rats.
  • Fluid from macrophages of short-fiber rats significantly increased fibroblast DNA synthesis (thymidine uptake) at both amounts tested. Fluid from macrophages of control or long-fiber rats had no effect.
  • Collagen synthesis by cultured fibroblasts was significantly increased by fluid from short-fiber macrophages. Fluid from control or long-fiber macrophages gave uptake no different from normal fibroblasts.
  • In vitro at 100 micrograms per ml, over 80% of normal macrophages ingested short fibers, compared with less than 30% that took up long fibers.
  • In vitro, fluid from macrophages exposed to the low dose (10 micrograms per ml) of either fiber had no effect on fibroblast DNA synthesis.
  • In vitro, fluid from macrophages exposed to 100 micrograms of short fibers significantly increased fibroblast proliferation at both 0.25 and 0.5 ml.
  • In vitro, fluid from macrophages incubated with long fibers produced a much smaller but significant increase in fibroblast DNA synthesis, at 0.5 ml.
  • In vitro, an approximately 30% increase in collagen-related proline uptake was found only in the 100-microgram short-fiber group. The authors did not show these data.
• The authors' conclusion: The authors concluded that macrophage growth-factor secretion after short fibers was not associated with fibrosis. Fibrosis developed after long fibers even though alveolar macrophage secretions from those lungs did not stimulate fibroblasts. In their view, long-fiber fibrosis is more likely related to growth factor secretion by interstitial rather than alveolar macrophages.
• Limitations the authors state:
  • The authors acknowledged that a macrophage-derived factor could have started the fibrotic process before the single 8-week time point examined, although they cite earlier studies indicating fibrosis was still increasing at 8 weeks.

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Alveolar Macrophage, Crocidolite, Pulmonary Fibrosis, Collagen, Phagocytosis, Fibrogenic, Cytokine.

Related studies

• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)
• Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease — R. Bégin, A. Dufresne, et al. (1989)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)
• Fibroblast growth factor-10 prevents asbestos-induced alveolar epithelial cell apoptosis by a mitogen-activated protein kinase-dependent mechanism — D. Upadhyay, V. Panduri, et al. (2005)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)

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