Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis

Our plain-English summary of Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis, by I. Lemaire, H. Beaudoin, S. Massé, et al (The American Journal of Pathology, 1986).

The study

• Authors: I. Lemaire, H. Beaudoin, S. Massé, C. Grondin
• Journal: The American Journal of Pathology
• Published: 1986;122(2):205-11
• Cited by: 79 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Asbestotic lesions are characterized by macrophagic accumulation, fibroblast proliferation, and collagen deposition. To evaluate the potential involvement of alveolar macrophages in the subsequent fibrogenic reaction, the authors studied the effects of macrophages from normal and asbestos-treated rats upon lung fibroblast proliferation in vitro. Culture supernatants from bronchoalveolar (BAL) cells (99% macrophages) of normal rats stimulated lung fibroblast DNA synthesis and growth in a dose-dependent manner. Fibroblast growth factor (FGF) release by alveolar macrophages (AMs) was rapid (within 1 hour of incubation) and dependent on the number of AMs in culture. Moreover, culture supernatants from BAL cells of animals exposed to asbestos (single intratracheal injection) stimulated fibroblast proliferation to a greater degree than culture supernatants from BAL cells of control animals. Enhanced FGF production occurred 1 week after asbestos instillation and persisted up to 24 weeks. This change was accompanied in the early stages (1-4 weeks) by an increase in the total number of BAL cells which returned to control values by 12 weeks. Differential analysis of BAL cell populations showed a transient infiltration of neutrophils in the bronchoalveolar compartment followed by a significant accumulation of macrophages which persisted up to 1 month. Furthermore, lungs of asbestos-treated animals showed evidence of pathologic alterations characterized by fibroblast proliferation and collagen deposition. This study demonstrates that increased production of fibroblast growth factor by alveolar macrophages in vitro coincides with the development of asbestos-induced fibrosis. Prolonged stimulation of FGF release may contribute to excessive fibroblast proliferation and fibrosis.

In plain English

This was a laboratory study in rats. The authors gave male Wistar rats a single injection into the windpipe of 5 mg of UICC chrysotile B asbestos, or saline for comparison. They examined at least 5 animals per group at intervals from 1 week to 24 weeks. They washed cells out of the lungs, mostly alveolar macrophages, and tested whether fluid from these cells in culture made lung fibroblasts grow. The fibroblasts used were human embryonic lung fibroblasts. Fluid from normal rat macrophages stimulated fibroblast growth at concentrations from 10% to 50%. In asbestos-exposed rats, neutrophils made up 23-30% of washed-out cells in the first week, followed by increased macrophage numbers up to 4 weeks. Macrophages from asbestos-exposed rats caused a threefold to fourfold increase in fibroblast thymidine uptake, a measure of cell division, compared with twofold for normal macrophages. This higher stimulation was still seen at 24 weeks. Lungs of exposed rats showed fibroblast proliferation from 7 days on. The authors concluded that increased release of this growth factor may contribute to fibroblast proliferation in asbestos lesions.

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 given asbestos or saline into the trachea) combined with laboratory (in vitro) tests of lung lavage cells on fibroblast growth
• Who was studied: Male Wistar rats (250-300 g) from Charles River Canada; at least 5 animals per group examined at intervals from 1 week to 24 weeks after instillation; Sherbrooke University, Quebec, Canada. Fibroblast growth was tested on human embryonic lung fibroblasts (WI-38).
• Exposure: Single transtracheal injection of 5 mg UICC standard chrysotile B asbestos suspended in saline; control rats received saline
• Main results:
  • Culture fluid from normal rat alveolar macrophages significantly stimulated fibroblast proliferation at concentrations from 10% to 50%; lower concentrations had no significant effect
  • In normal rat macrophage cultures, fibroblast growth-promoting activity was detectable after 1-2 hours and maximal by 4 hours
  • In asbestos-exposed rats, total lavage cell numbers were significantly higher than in saline-exposed rats in the first weeks; by week 4 they were still significantly higher but decreasing, and returned to normal thereafter
  • During the first week after asbestos exposure, neutrophils made up 23-30% of lavage cells; their proportion returned to normal at 2 weeks
  • In asbestos-exposed rats, the absolute number of macrophages increased significantly, lasting up to 4 weeks after exposure
  • A small but significant increase in lymphocytes was seen in asbestos-exposed rats 12 weeks after exposure
  • Culture fluid from normal rat macrophages stimulated fibroblast thymidine incorporation twofold; fluid from macrophages of asbestos-treated rats produced a threefold to fourfold stimulation
  • The significantly higher stimulation of fibroblast replication by macrophages from asbestos-exposed rats was still seen up to 24 weeks after exposure
  • Lungs of asbestos-exposed rats showed lesions around the terminal bronchioles with fibroblast proliferation in surrounding tissue, seen from 7 days onward
• The authors' conclusion: The authors concluded that their observations suggest increased release of fibroblast growth factor by alveolar macrophages may contribute to the fibroblast proliferation seen in asbestos lesions
• Limitations the authors state:
  • The authors state that the growth-promoting factor released by the rat macrophages was not fully identified and needs further characterization

Topics

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

Related studies

• Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages — I.Y. Adamson, D.H. Bowden (1990)
• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes 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)
• Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis — I. Lemaire, C. Dubois, et al. (1986)
• Differential proliferation of rat lung fibroblasts induced by the platelet-derived growth factor-AA, -AB, and -BB isoforms secreted by rat alveolar macrophages — J.C. Bonner, A.R. Osornio-Vargas, et al. (1991)
• Asbestos stimulates alveolar macrophages to release a factor causing human lung fibroblasts to replicate — P. Bitterman, S. Rennard, et al. (1981)

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