Asbestos and silica-induced changes in human alveolar macrophage phenotype

Our plain-English summary of Asbestos and silica-induced changes in human alveolar macrophage phenotype, by A. Holian, M.O. Uthman, T. Goltsova, et al (Environmental Health Perspectives, 1997).

The study

• Authors: A. Holian, M.O. Uthman, T. Goltsova, S.D. Brown, R.F. Hamilton
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1139-42
• Cited by: 45 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The mechanism by which fibrogenic particulates induce inflammation that can progress to lung fibrosis is uncertain. The alveolar macrophage (AM) has been implicated in the inflammatory process because of its function and reported release of inflammatory mediators when isolated from fibrotic patients. It has been recently shown that fibrogenic, but not nonfibrogenic, particulates are highly potent in inducing apoptosis of human AM. In this study, we tested the hypothesis that fibrogenic particulates could shift the phenotypic ratio of human AM to a more inflammatory condition. The macrophage phenotypes were characterized by flow cytometry targeting the RFD1 and RFD7 epitopes. Results demonstrated that chrysotile and crocidolite asbestos, as well as crystalline silica, but not titanium dioxide or wollastonite, increased the RFD1+ phenotype (inducer or immune activator macrophages) and decreased the RFD1+ RFD7+ phenotype (suppressor macrophages). These results provide a mechanistic explanation that may link apoptosis (namely, suppressor macrophages) to a shift in the ratio of macrophage phenotypes that could initiate lung inflammation.

In plain English

This was a laboratory (test-tube) study of lung cells, not a study of people's health. The authors collected alveolar macrophages, immune cells from the lung's air sacs, by lung washing from normal, nonsmoking adult volunteers. They incubated the cells for 4 or 24 hours with chrysotile asbestos, crocidolite asbestos, crystalline silica, titanium dioxide, wollastonite, or no particles. They measured RFD1 and RFD7 markers, which identify macrophage types. In 12 normal subjects, 5% of cells were RFD1-positive, 43% carried both markers and 5% were RFD7-positive. Chrysotile, crocidolite and silica, but not titanium dioxide or wollastonite, increased RFD1-positive cells (inducer or immune activator macrophages) and decreased cells carrying both markers (suppressor macrophages). The fibrogenic particles also decreased RFD7-positive cells. The authors proposed that death (apoptosis) of suppressor macrophages might explain this shift, which could start lung inflammation. However, the study did not show that suppressor macrophages were preferentially dying; the authors wrote this remained to be established. They noted their conclusions assume these cell types are fixed, and that the shift's relevance to lung fibrosis remains undetermined.

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 human lung immune cells (alveolar macrophages)
• Who was studied: Alveolar macrophages obtained by bronchoalveolar lavage (lung washing) from normal, nonsmoking adult volunteers of either sex, at the University of Texas Houston Health Science Center. Baseline cell types were measured in 12 subjects. Particle experiments used cells from 10 subjects (crocidolite, silica) or 8 subjects (chrysotile, titanium dioxide, wollastonite). Dates are not stated.
• Exposure: Cells were incubated for 4 or 24 hours with no particles or with one of five particles. The doses were chosen to have approximately equal surface area: chrysotile 25, crocidolite 75, crystalline silica 133, titanium dioxide 60 and wollastonite 200 (per millilitre; the mass unit is garbled in the scan). Chrysotile, crocidolite and silica were grouped as fibrogenic; titanium dioxide and wollastonite were grouped as nonfibrogenic.
• Main results:
  • In unexposed cells from 12 normal subjects, the percentages of RFD1-positive, RFD1 and RFD7 double-positive, and RFD7-positive macrophages were 5, 43 and 5, respectively.
  • Chrysotile, crocidolite and crystalline silica, but not titanium dioxide or wollastonite, increased RFD1-positive cells (inducer or immune activator macrophages) and decreased RFD1 and RFD7 double-positive cells (suppressor macrophages).
  • The fibrogenic particles (chrysotile, crocidolite, silica) also decreased RFD7-positive cells.
  • Results were expressed relative to unexposed cells from the same subject. They were averaged over 10 subjects for crocidolite and silica and over 8 subjects for chrysotile, titanium dioxide and wollastonite.
• The authors' conclusion: The authors concluded that their results provide a mechanistic explanation that may link apoptosis (cell death) of suppressor macrophages to a shift in the ratio of macrophage types that could initiate lung inflammation. The study did not show that suppressor macrophages were the cells dying.
• Limitations the authors state:
  • It had not been shown that the suppressor (double-positive) cells are more sensitive to apoptosis than the RFD1-positive cells.
  • The conclusions assume the macrophage types are fixed. If cells can change type, the particles might shift the ratio without causing cell death.
  • Shifts in these cell types have been reported in lung inflammation, but whether the same holds for lung fibrosis remains to be determined.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Fibrogenic, Inflammation, Fibrosis, Apoptosis, Macrophage, Chrysotile, Crocidolite.

Related studies

• Involvement of the ICE family of proteases in silica-induced apoptosis in human alveolar macrophages — R. Iyer, A. Holian (1997)
• Mechanisms associated with human alveolar macrophage stimulation by particulates — A. Holian, K. Kelley, et al. (1994)
• Rapid screening of possible cytotoxic effects of particulate air pollutants by measurement of changes in cytoplasmic free calcium, cytosolic pH, and plasma membrane potential in alveolar macrophages by flow cytometry — A. Tárnok, M. Dörger, et al. (2001)
• Asbestos induces apoptosis in human alveolar macrophages — R.F. Hamilton, L.L. Iyer, et al. (1996)
• A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function — R.F. Hamilton, A. Holian, et al. (2004)
• Silica binds serum proteins resulting in a shift of the dose-response for silica-induced chemokine expression in an alveolar type II cell line — E.G. Barrett, C. Johnston, et al. (1999)

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