Inorganic particles induce secretion of a macrophage homologue of platelet-derived growth factor in a density-and time-dependent manner in vitro

Our plain-English summary of Inorganic particles induce secretion of a macrophage homologue of platelet-derived growth factor in a density-and time-dependent manner in vitro, by R.M. Schapira, A.R. Osornio-Vargas, A.R. Brody (Experimental Lung Research, 1991).

The study

• Authors: R.M. Schapira, A.R. Osornio-Vargas, A.R. Brody
• Journal: Experimental Lung Research
• Published: 1991;17(6):1011-24
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The inhalation of inorganic dust can lead to the development of interstitial pulmonary fibrosis, characterized by the accumulation of fibroblasts and connective tissue matrix in the lung interstitium. The fibrosis causes alterations in the architecture of the lung parenchyma, resulting in abnormal gas exchange and hypoxemia. In a rat model of asbestos exposure, inhaled fibers are deposited on alveolar duct bifurcations, followed by an accumulation of alveolar macrophages at the sites of dust deposition. The alveolar macrophage is thought to be a major mediator of the pulmonary inflammatory response to inhaled dust. Platelet-derived growth factor (PDGF) is a cytokine that has potent chemotactic and mitogenic effects on mesenchymal cells, such as fibroblasts and smooth muscle cells. We studied the secretion of an alveolar macrophage-derived homologue of PDGF in response to carbonyl iron spheres or chrysotile asbestos fibers in vitro. We demonstrate here that rat alveolar macrophages attached to a plastic substrate produce 69 +/- 79 picograms (pg) of PDGF per 10 million macrophages. This is similar to amounts recovered from human platelets. In contrast, macrophages exposed to iron spheres secrete 429 +/- 177 pg of PDGF/10(6) macrophages after 24 h in culture. Exposure to asbestos fibers increased the PDGF production to 628 +/- 213 pg/10(6) cells. PDGF secretion was influenced by the particles in a density- and time-dependent manner. We hypothesize that PDGF and other cytokines secreted by macrophages mediate the development of dust-induced lung disease.

In plain English

This cell-culture study tested whether dust makes rat alveolar macrophages (cells that engulf inhaled particles) release a form of platelet-derived growth factor (PDGF). PDGF stimulates fibroblasts, which are cells involved in lung scarring. Macrophages washed from male rats' lungs were cultured untreated, with carbonyl iron spheres (described as nonfibrogenic), or with chrysotile asbestos fibers. After 24 hours, untreated cells released on average 69 picograms of PDGF per million macrophages. Cells given iron at 1000 micrograms per square centimetre released 429, significantly more. PDGF release from iron-treated cells rose with iron density and with time, and was undetectable at 4 hours. With asbestos at 7.5, 15 and 30 micrograms per square centimetre, average release was 104, 284 and 628 picograms per million cells, against 94 for untreated cells in that experiment. At 60 it fell to 58, which the authors assumed was due to asbestos harming the cells. The authors hypothesized that PDGF and other macrophage products mediate dust-induced lung fibrosis. They said they did not yet know whether asbestos producing more PDGF than iron was biologically relevant.

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: Laboratory (in vitro) experiment on rat alveolar macrophages in cell culture
• Who was studied: Alveolar macrophages obtained by lung lavage from 8- to 10-week-old CD male rats from Charles River Laboratories, Raleigh, NC. The number of rats is not stated. Each asbestos experiment, and the standard iron exposure, was performed 2-4 times.
• Exposure: Carbonyl iron powder (spheres) and chrysotile asbestos from the Jeffrey Mine, Quebec, added to cultures for 24 hours. Iron was given at 200, 1000 and 2000 micrograms per square centimetre, with 1000 as the standard density. Chrysotile was given at 7.5, 15, 30 and 60 per square centimetre of culture area. A time-course experiment with iron at 1000 collected medium at 4, 8, 16 and 24 hours.
• Main results:
  • Untreated (control) macrophages secreted PDGF ranging from 0 to 215 pg per million cells, with a mean of 69 and SD of 79.
  • Macrophages treated with carbonyl iron at 1000 micrograms per square centimetre for 24 h secreted 247 to 623 pg PDGF per million macrophages (mean 429, SD 177). This was significantly more than control macrophages (P less than .05).
  • In the time-course experiment with iron-exposed macrophages, PDGF was not detected at 4 h. It measured 169 pg per million cells at 8 h, 300 at 16 h and 560 at 24 h. Control macrophages secreted no detectable PDGF in this experiment.
  • With iron at 200, 1000 and 2000 micrograms per square centimetre, PDGF secretion at 24 h was density-dependent (r = .985; P = .02).
  • With chrysotile asbestos for 24 h, PDGF secretion per million macrophages rose with density. At 7.5 it was 69-130 pg (mean 104, SD 32). At 15 it was 222-346 pg (mean 284, SD 88). At 30 it was 477-779 pg (mean 628, SD 213). Control cells in this experiment yielded 94 pg.
  • At 60 per square centimetre of chrysotile, PDGF secretion decreased to 58 pg per million macrophages. The authors attributed this, probably, to asbestos-induced cytotoxicity.
  • No PDGF was detectable in lysed macrophages (control or iron-exposed) at 8 or 24 h. The authors took this to suggest PDGF is actively secreted rather than stored.
  • Scanning electron microscopy showed the macrophages engulfed both iron spheres and chrysotile fibers. Cells remained viable through the culture period.
• The authors' conclusion: The authors concluded that rat alveolar macrophages exposed to carbonyl iron or chrysotile asbestos in vitro secrete PDGF in a density-dependent manner, with asbestos causing more PDGF secretion than iron at the densities studied. They hypothesized that PDGF and other cytokines secreted by the stimulated macrophages mediate dust-induced pulmonary fibrogenesis.
• Limitations the authors state:
  • Meaningful comparison between particle types with very different surface areas and densities needs further study. The authors do not know if the greater PDGF secretion with asbestos than with iron is biologically relevant.
  • The number of particles interacting with or taken into the cells was not quantified for either dust.
  • The drop in PDGF at the highest asbestos density was assumed, not shown, to be due to cytotoxicity.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

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

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

Related studies

• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)
• 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)
• 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)
• Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore — S. Kouzan, A.R. Brody, et al. (1985)
• Paradoxical effects of platelet-derived growth factor-A overexpression in malignant mesothelioma. Antiproliferative effects in vitro and tumorigenic stimulation in vivo — L.J. Metheny-Barlow, B. Flynn, et al. (2001)
• 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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