Monocyte-derived growth factors in asbestos-induced interstitial fibrosis

Our plain-English summary of Monocyte-derived growth factors in asbestos-induced interstitial fibrosis, by D.A. Schwartz, L. Rosenstock, J.G. Clark (Environmental Research, 1989).

The study

• Authors: D.A. Schwartz, L. Rosenstock, J.G. Clark
• Journal: Environmental Research
• Published: 1989;49(2):283-94
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003845).

Abstract

Asbestos-induced pulmonary fibrosis is thought to result from a series of cellular interactions involving the alveolar macrophage and the lung fibroblast. Although a dose-response relation has been established between asbestos exposure and the development of interstitial fibrosis, the majority of workers exposed even to high concentrations of asbestos do not develop radiographically evident interstitial fibrosis. As a means of understanding the pathogenesis of asbestos-induced fibrosis and the differential host response to the asbestos fiber, we studied the production of monocyte-derived growth factors in subjects with asbestosis (N = 5) and normal exposure-matched controls (N = 5). Under unstimulated culture conditions, the conditioned medium (CM) from monocytes from control subjects had a greater proliferative effect on fibroblasts than monocyte CM from patients with asbestosis. With CM from concanavalin A-stimulated monocytes, the proliferative response of the fibroblast was similar in those with asbestosis and control subjects. Freshly isolated monocytes from both normal subjects and patients with asbestosis did not express the gene for the B chain of platelet-derived growth factor (PDGF) as evaluated by hybridization with a PDGF-specific human cDNA probe. After 20 hr of culture in concanavalin A, monocytes from normal subjects expressed the gene for the B chain of PDGF while, under the same culture conditions, none of the monocyte preparations from patients with asbestosis produced mRNA for this growth factor. These data indicate that peripheral blood monocytes from patients with asbestosis compared to exposure-matched controls have a reduced capacity to produce growth factor activity as measured by mitogenic activity and mRNA levels for the B chain of PDGF. These results suggest that peripheral blood monocytes from patients with asbestosis may comprise a less mature population of cells compared to exposure-matched controls.

In plain English

This was a small case-control laboratory study of blood cells from asbestos-exposed men in a University of Washington health surveillance program. Five nonsmoking Caucasian men with asbestosis were compared with five exposure-matched controls who had normal chest X-rays and breathing tests. The authors grew monocytes (a type of white blood cell) from each man's blood, with and without a stimulant called concanavalin A. They then tested whether fluid from these cultures made fibroblast cells grow. Without stimulation, fluid from the controls' monocytes produced more fibroblast growth than fluid from the asbestosis patients' monocytes during the first 4 days. With stimulation, the two groups were similar. Freshly isolated monocytes from both groups did not show activity of the gene for the B chain of platelet-derived growth factor (PDGF). After 20 hours of stimulation, this gene activity was detected in all of the controls' monocyte samples but in none from the asbestosis patients. The authors concluded that this may reflect a less mature population of circulating monocytes in people with asbestosis.

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: case-control laboratory study (cells cultured from blood samples)
• Who was studied: Asbestos-exposed workers from a health surveillance program at the University of Washington's Harborview Occupational Medicine Program in Seattle. Only nonsmoking Caucasian men were eligible. There were 5 men with asbestosis and 5 exposure-matched controls with normal chest X-rays and spirometry. Controls were matched within 10 years for age and for asbestos exposure duration and latency. About 60% of persons contacted agreed to take part.
• Exposure: Occupational asbestos exposure; the fiber type is not stated. Cases needed at least 5 years of exposure and at least 15 years since first exposure. Mean exposure duration was 22.4 years for the asbestosis group and 30.0 years for controls. In the laboratory, monocytes were cultured with and without concanavalin A (10 micrograms/ml).
• Main results:
  • Without stimulation, conditioned medium from control subjects' monocytes had a greater effect on fibroblast growth than that from asbestosis patients' monocytes, during the first 4 days of culture. At day 2, growth was 424.9 plus or minus 136.3 percent above baseline for controls versus 186.3 plus or minus 17.1 for asbestosis patients.
  • With concanavalin A stimulation, fibroblast growth was similar for the asbestosis group and the controls.
  • Within the asbestosis group, monocytes tended to produce more growth factor activity with concanavalin A than without it during the first 6 days of culture (P value 0.05 at days 2, 4 and 6). Controls' monocytes did not show this increase.
  • Freshly isolated monocytes from both groups did not express the gene for the B chain of PDGF.
  • After 20 hours with concanavalin A, all monocyte preparations from the controls had detectable mRNA for the B chain of PDGF. None from the 5 asbestosis patients did.
  • The asbestosis patients tended to have lower total white cell counts than controls (mean 5670.0 vs 7090.0; P = 0.09, not statistically significant). They also had a slightly lower percentage of monocytes (7.1% vs 8.7%; P = 0.28).
• The authors' conclusion: The authors had expected monocytes from people with asbestosis to produce more growth factors, but their analysis did not show this in blood monocytes. They concluded that the reduced growth factor production by monocytes from people with asbestosis may reflect a less mature population of circulating blood monocytes.
• Limitations the authors state:
  • After 4 days of culture, monocyte viability fell below 50% in all culture wells. The authors say this may explain why differences between the groups faded after day 4.
  • Controls' monocytes did not respond to concanavalin A. The authors say this could have resulted from the cells being stimulated during the separation procedure.
  • The study included no people who had not been exposed to asbestos. The authors say comparisons with monocytes from nonexposed individuals are needed.

Topics

Medical terms in this study, explained in our Lexicon: Interstitial Fibrosis, Pulmonary Fibrosis, Alveolar Macrophage, Fibroblast, Dose-response relationship, Asbestos Exposure, Fibrosis, Platelet-Derived Growth Factor (PDGF).

Related studies

• 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)
• Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas — L.A. Goodglick, C.A. Vaslet, et al. (1997)
• The pathobiology of asbestos-induced lung disease: a proposed role for macrophage-derived growth factors — J.A. Lasky, J.C. Bonner, et al. (1991)
• SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment — P. Cheresh, S.J. Kim, et al. (2021)
• 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)
• Susceptibility to asbestos-induced and transforming growth factor-beta1-induced fibroproliferative lung disease in two strains of mice — G.S. Warshamana, D.A. Pociask, et al. (2002)

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