In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos

Our plain-English summary of In vitro suppression of fibroblast growth inhibitory lymphokine production by asbestos, by I. Lemaire, C. Dubois (Clinical and Experimental Immunology, 1983).

The study

• Authors: I. Lemaire, C. Dubois
• Journal: Clinical and Experimental Immunology
• Published: 1983;53(1):239-48
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Human peripheral blood mononuclear leucocytes (PBML) stimulated with concanavalin A (Con A) or phytohaemagglutinin (PHA) produced a soluble factor which inhibits lung fibroblast DNA synthesis and growth. Lymphocyte enriched preparations produced significant growth inhibitory activity in the presence of PHA whereas media from adherent mononuclear cells incubated in the presence of the mitogen did not contain similar activity. This fibroblast growth inhibitory factor (FGIF) was non-dialysable, heat stable and resistant to pH 5. FGIF was also resistant to treatment with chymotrypsin and phosphodiesterase but partially sensitive to treatment with trypsin. Interestingly, there was significant suppression of FGIF production by PBML cultured with PHA in the presence of low concentrations of chrysotile asbestos (5-25 micrograms/ml). In this regard, asbestos (25 micrograms/ml) was not cytotoxic for lymphocytes but had a damaging effect on monocytes as evidenced by the release of lactate dehydrogenase (LDH) a cytoplasmic enzyme, in their culture media. These findings indicate that stimulated lymphocytes have the ability to inhibit fibroblast proliferation by releasing FGIF and that asbestos interfere with this process. Thus, while FGIF may regulate the extent of connective tissue proliferation during normal repair process, suppression of its production by asbestos may contribute to excessive fibroblast accumulation and fibrosis.

In plain English

In this laboratory study at the Université de Sherbrooke, Quebec, the authors stimulated human blood white cells (mononuclear leucocytes) with phytohaemagglutinin (PHA) or concanavalin A. Fluid from the stimulated cells slowed DNA synthesis and growth of human embryonic lung fibroblasts. In a typical experiment, DNA synthesis was inhibited by 85%, compared with 20% for fluid from unstimulated cells. The authors called the responsible substance fibroblast growth inhibitory factor (FGIF). It came mainly from lymphocytes, and fluid from purified monocytes had no significant effect. When the blood cells were stimulated in the presence of chrysotile asbestos (UICC Canadian chrysotile B, 5 to 25 micrograms per millilitre), less FGIF was made, and the effect was dose-dependent. Fluid from cells exposed to 25 micrograms per millilitre inhibited fibroblast proliferation by 38%, against 83% without asbestos. Chrysotile did not make lymphocytes release more LDH, a sign of cell membrane damage, but purified monocytes released 80% more. The authors concluded that asbestos suppresses this regulation of fibroblasts. They stated that whether this contributes to asbestosis requires further investigation.

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 using human blood cells and a human lung fibroblast cell line; no people or animals were studied for disease
• Who was studied: Human peripheral blood mononuclear leucocytes (PBML), separated into lymphocyte-enriched and monocyte fractions, and human embryonic lung fibroblasts (WI-38 cell line); Université de Sherbrooke, Quebec, Canada. The number of blood donors is not reported.
• Exposure: UICC Canadian chrysotile B asbestos added to PHA-stimulated blood cells at 0 to 25 micrograms per millilitre for 48 hours. 25 micrograms per millilitre was used in the cell-damage (LDH) tests.
• Main results:
  • In a typical experiment, fluid from lectin-stimulated blood cells inhibited fibroblast DNA synthesis (thymidine incorporation) by 85% at 48 hours, compared with 20% for fluid from non-stimulated blood cells
  • The reduced DNA synthesis was accompanied at 72 hours by a statistically significant reduction in fibroblast number
  • The lymphocyte-enriched population accounted for most of the inhibiting activity. Fluid from purified monocytes did not significantly inhibit fibroblast proliferation.
  • FGIF passed through dialysis unchanged and resisted heating to 56°C for 30 minutes. It was resistant to chymotrypsin and phosphodiesterase but partially sensitive to trypsin.
  • Chrysotile reduced FGIF production in a dose-dependent manner. Fluid from PHA-stimulated blood cells exposed to 25 micrograms per millilitre chrysotile inhibited fibroblast proliferation by 38%, compared with 83% for fluid prepared without asbestos.
  • With chrysotile at 25 micrograms per millilitre, the lymphocyte-enriched population released no more LDH than untreated cultures. Unfractionated blood cells released 30% more LDH and purified monocytes released 80% more.
• The authors' conclusion: The authors concluded that stimulated lymphocytes can inhibit lung fibroblast proliferation and that asbestos suppresses this regulation. They suggested the suppression may be partly related to damage to monocytes.
• Limitations the authors state:
  • Whether this action of asbestos contributes to asbestosis was not established and requires further investigation
  • The mechanism by which asbestos suppresses FGIF production is unknown
  • The chemical identity of FGIF (whether it is lymphotoxin, interferon or something else) is not known

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Chrysotile, Lactate Dehydrogenase (LDH), Fibrosis.

Related studies

• Immunoregulation of lung fibroblast growth: alteration in asbestos-induced pulmonary fibrosis — I. Lemaire, C. Dubois, et al. (1986)
• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Chrysotile asbestos stimulates platelet-derived growth factor-AA production by rat lung fibroblasts in vitro: evidence for an autocrine loop — J.A. Lasky, P.G. Coin, et al. (1995)
• Early-passage rat lung fibroblasts do not migrate in vitro to transforming growth factor-beta — A.R. Osornio-Vargas, V.G. Kalter, et al. (1993)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts — J.C. Bonner, A.L. Goodell, et al. (1993)

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