Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis

Our plain-English summary of Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis, by I. Lemaire, C. Dubois, C. Grondin, et al (Clinical and Experimental Immunology, 1986).

The study

• Authors: I. Lemaire, C. Dubois, C. Grondin, D. Gingras
• Journal: Clinical and Experimental Immunology
• Published: 1986;66(1):201-8
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Initial studies on mononuclear cell-fibroblast interactions have shown that stimulated human lymphocytes produced a fibroblast growth inhibitory factor and that asbestos, a fibrogenic dust, interferes with this process in vitro. To investigate the role of these interactions in pathologies characterized by pulmonary fibrosis, we used a rat model of asbestos-induced fibrosis. Rats received a single intratracheal instillation of either saline or 10 mg of chrysotile asbestos fibres. Three months after treatment, peripheral blood mononuclear leucocytes (PBML) supernatant fractions were prepared and their effects on lung fibroblast growth measured. As for human PBML, rat PBML stimulated with Concanavalin A (Con A) produced 24 h after initiation of the cultures a soluble factor which inhibits lung fibroblast DNA synthesis and growth in a dose-dependent fashion. By contrast, Con A-stimulated PBML from rats exposed to asbestos failed to produce significant levels of fibroblast growth inhibitory activity. No significant change of total PBML number or in the proportion of circulating mononuclear cell populations was observed. Furthermore, upon stimulation with lipopolysaccharide (LPS), monocytes from asbestotic animals retained their capacity to produce interleukin (IL-1), a mediator required for lymphokine production. Our study demonstrates that suppression of FGIF production by circulating PBML occurs in animals with lung fibrosis and suggests that mechanisms other than impairment of IL-1 production may be responsible for the suppressive effect of asbestos on the production of such fibroblast regulatory lymphokine.

In plain English

In this animal experiment, the authors gave male Wistar rats a single injection into the windpipe of either saline (8 rats) or 10 mg of UICC chrysotile B asbestos (9 rats). Three months later, all asbestos-treated rats had lung lesions, described as extensive fibrosis, while saline-treated rats showed no fibrosis. The authors cultured blood white cells (peripheral blood mononuclear leucocytes) from each rat, stimulated them with Concanavalin A, and tested whether the culture fluid slowed the growth of lung fibroblasts, the cells that form scar tissue. Fluid from saline-treated rats reduced fibroblast DNA synthesis by 45%, compared with 9% for unstimulated cells, and lowered fibroblast numbers. Fluid from asbestos-exposed rats failed to inhibit fibroblast growth. Blood cell counts and proportions did not differ significantly between groups. Monocytes from both groups made interleukin 1 when stimulated. The authors concluded that this suppression occurs in animals with lung fibrosis. They stated that whether it contributes to fibrosis or results from it remains to be clarified.

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, followed by laboratory cell-culture assays)
• Who was studied: Male Wistar rats weighing 250 to 300 g, from Charles River Canada. The study was done at the Université de Sherbrooke, Quebec. Group sizes in the tables were 8 saline-treated and 9 asbestos-treated rats.
• Exposure: A single intratracheal instillation of 10 mg of UICC standard chrysotile B asbestos (21% of fibres longer than 10 micrometres), compared with saline. Animals were killed 3 months after instillation.
• Main results:
  • In saline-treated (control) rats, fluid from stimulated blood mononuclear cells inhibited lung fibroblast DNA synthesis by 45%, compared with 9% for unstimulated cell fluid. Fibroblast numbers at 72 h averaged 5 x 10^4 with stimulated fluid, compared with 8.5 x 10^4 with unstimulated fluid and 8.3 x 10^4 with control media.
  • In asbestos-exposed rats, fluid from stimulated blood mononuclear cells did not inhibit fibroblast growth. There was no significant difference in DNA synthesis or cell counts compared with control medium.
  • Total blood mononuclear cell numbers did not change significantly, averaging 13 x 10^6 cells in both saline- and asbestos-exposed rats. The proportions of lymphocytes, monocytes and neutrophils also did not differ between the two groups.
  • Three months after chrysotile B instillation, rat lungs showed extensive fibrosis, and all asbestos-treated animals were affected (lesion incidence 100% of 9). Saline-treated rats showed no fibrosis (0% of 8).
  • When stimulated with lipopolysaccharide, monocytes from both saline- and asbestos-exposed rats produced significant interleukin 1 activity, with no significant difference between the groups.
• The authors' conclusion: The authors concluded that suppression of fibroblast growth inhibitory factor production by circulating blood mononuclear cells occurs in rats with asbestos-induced lung fibrosis. They suggested that mechanisms other than impaired interleukin 1 production may be responsible.
• Limitations the authors state:
  • The authors stated it remains unclear whether the suppression contributes to the development of fibrosis or is a consequence of the disease.
  • The authors stated their results do not exclude a role for monocytes or macrophages in the suppression.

Topics

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

Medical terms in this study, explained in our Lexicon: Fibroblast, Pulmonary Fibrosis, Fibrogenic, Fibrosis, Chrysotile.

Related studies

• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos — I. Lemaire, C. Dubois (1983)
• 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)
• Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats — T.D. Perdue, A.R. Brody (1994)
• 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)

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