Pulmonary and systemic immunoregulatory changes during the development of experimental asbestosis

Our plain-English summary of Pulmonary and systemic immunoregulatory changes during the development of experimental asbestosis, by M. Rola-Pleszczynski, S. Gouin, R. Bégin (Clinical and Experimental Immunology, 1984).

The study

• Authors: M. Rola-Pleszczynski, S. Gouin, R. Bégin
• Journal: Clinical and Experimental Immunology
• Published: 1984;58(2):325-34
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Initial studies on the effects of low dose exposure to asbestos on pulmonary and systemic immune responses have revealed a bi-phasic pattern characterized by an early enhancement followed by inhibition of lymphocyte responses to several mitogens. In the present study, we sought to define the cellular and humoral factors, responsible for the observed effects. The early enhancement of peripheral blood and pulmonary lymphocyte responses to mitogens may be due, at least in part, to the loss of the inhibitory capacity of alveolar macrophages from asbestos exposed animals to suppress lymphocyte response. Furthermore, macrophages from low dose exposed animals actually enhanced lymphocytes responses to Con A and PHA. The latter inhibition observed following 6-12 months of exposure may be due to the in vivo generation of suppressor lymphocytes. Unfractionated lymphocytes from blood or alveolar space as well as enriched T cells from high dose exposed animals suppressed the proliferative responses of pulmonary or circulating lymphocytes to PHA and Con A, but not to PWM. Similarly, pre-incubation of normal blood or pulmonary lymphocytes in serum from high dose exposed animals for 24 h induced the appearance of suppressor cell activity in these populations when further tested in a co-culture assay with normal fresh lymphocytes. Taken together, these studies demonstrate the multi-faceted effects of asbestos on the immune system. The eventual fibrogenic process of asbestosis may result from the interplay of several mechanisms, some of which are suggested in this work.

In plain English

This was a laboratory experiment in sheep, from the Université de Sherbrooke in Quebec, on how asbestos changes immune cells during experimental asbestosis. Male sheep, five per dose, had UICC Canadian chrysotile B asbestos put directly into the windpipe: 0 mg (controls), 10 mg (low dose) or 100 mg (high dose). This was done monthly for 6 months, then weekly from the 6th to the 12th month. Lung and blood immune cells were then tested in culture. Larger numbers of lung macrophages from normal sheep held back lymphocyte responses to stimulants. Macrophages from low-dose sheep instead boosted responses to two stimulants, Con A and PHA. Macrophages from high-dose sheep neither held responses back nor boosted them. Blood cells from high-dose sheep suppressed normal cells' responses to Con A and PHA but not to a third stimulant, PWM. Normal blood cells kept for 24 hours in high-dose sheep serum suppressed responses to all three. The authors concluded that macrophage changes occur early, and that later, suppressor T cells are activated, probably by serum factors. They did not rule out other mechanisms.

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 (sheep exposed to asbestos, with laboratory tests of their lung and blood immune cells)
• Who was studied: Male sheep from commercial flocks, aged 18 to 30 months, five per dose group (control, low dose, high dose); research units at the Université de Sherbrooke, Quebec; dates not given
• Exposure: UICC Canadian chrysotile B asbestos given by intratracheal instillation: 0 mg (controls), 10 mg (low dose) or 100 mg (high dose) in 50 ml of buffered saline, monthly for the first 6 months, then weekly from the 6th to the 12th month
• Main results:
  • In normal sheep, low numbers of alveolar macrophages (1 per 100 blood lymphocytes) stimulated lymphocyte responses to Con A and PWM, while higher numbers were inhibitory
  • Adding indomethacin, a prostaglandin synthesis blocker, significantly enhanced responses of normal lung cells (FAC) to Con A and PWM, but had no significant effect on normal blood cells
  • Alveolar macrophages from low-dose sheep did not suppress blood lymphocyte responses, and significantly enhanced responses to Con A and PHA at a ratio of 10 lymphocytes to 1 macrophage
  • Alveolar macrophages from high-dose sheep also failed to suppress blood lymphocyte responses, but were not stimulatory either
  • Blood cells from high-dose sheep, cultured in normal serum, showed a significant decrease in response to Con A and PHA, but not PWM, compared with normal blood cells
  • Normal blood cells pre-incubated for 24 hours in serum from high-dose sheep became able to significantly suppress normal blood cell responses to all three mitogens
  • Blood cells from high-dose sheep significantly suppressed normal blood cell responses to Con A or PHA. T cells from high-dose sheep and high-dose lung lymphocytes also suppressed normal responses. None of these three cell populations suppressed responses to PWM.
• The authors' conclusion: The authors concluded that asbestos acts on local and systemic immunity in several ways. In their view, increased promotion and reduced suppression of lymphocyte responses by macrophages occur early in exposure. At later stages, suppressor T cells are activated, probably through the action of serum factors.
• Limitations the authors state:
  • The early phase of enhanced activity was short in their animal model, and the authors said explaining it further would need more experiments
  • The authors did not exclude other mechanisms for the later depressed responses: direct inhibition of lymphocytes by the fibers, or impaired macrophage helper function
  • The authors said it was unclear why responses to PWM were relatively unaffected by the suppressor cells

Topics

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

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Macrophage, Fibrogenic.

Related studies

• Cytokine regulation of lung fibroblast proliferation. Pulmonary and systemic changes in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)
• Experimental asbestosis. The development of lung cancer in rats with pulmonary deposits of chrysotile asbestos dust — P. Gross, R.T. DeTreville, et al. (1967)
• Chrysotile-induced asbestosis: changes in the free cell population, pulmonary surfactant and whole lung tissue of rats — T.D. Tetley, P.M. Hext, et al. (1976)
• Excessive accumulation of asbestos fibre in the bronchoalveolar space may be a marker of individual susceptibility to developing asbestosis: experimental evidence — R. Bégin, P. Sébastien (1989)
• Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests — R. Bégin, M. Rola-Pleszczynski, et al. (1983)
• Biochemical changes and pulmonary response of guinea pigs to asbestos dust — J. Singh, M.U. Beg, et al. (1976)

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