A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function

Our plain-English summary of A comparison of asbestos and urban particulate matter in the in vitro modification of human alveolar macrophage antigen-presenting cell function, by R.F. Hamilton, A. Holian, M.T. Morandi (Experimental Lung Research, 2004).

The study

• Authors: R.F. Hamilton, A. Holian, M.T. Morandi
• Journal: Experimental Lung Research
• Published: 2004;30(2):147-62
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The mechanism for how inhaled particles cause or exacerbate human diseases is not known. It is clear, however, that some particles are more bioactive than others. One possible mechanism may involve a modification of antigen-presenting cell function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole) and PM(2.5) (an urban particle) were cultured with human alveolar macrophages (HAMs) to determine whether antigen-presenting cell (APC) function was altered. HAMs were exposed to the bioactive particles, asbestos and PM(2.5), for 24 hours, then isolated free of extracellular particulates and nonviable cells. Isolated HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using tetanous toxoid as the antigen and the resulting culture supernatants were assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type, up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNgamma), and the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL-13). PM(2.5) exposure up-regulated all 3 cytokines also. Although cytokine production levels were significantly higher for the treatment compared to control cultures as a group, there was extreme variability in the responses between subjects. In addition, there was no correlation between an individual's cells' response to asbestos verses PM, suggesting that more than one possible mechanism exists for a particle-induced APC effect and individual differential sensitivities to inhaled bioactive particles. This work supports the hypothesis that some inhaled particles can modify immune function by directly affecting APCs thus up-regulating the normal lymphocyte response to antigens in the lung.

In plain English

This laboratory study tested whether asbestos and urban air particles change how human lung immune cells (alveolar macrophages) present an antigen to lymphocytes. Macrophages were collected by lung lavage from normal, nonsmoking volunteers. They were exposed for 24 hours to crocidolite, to Libby amphibole from the Libby, Montana vermiculite mine, or to the water-insoluble fraction of urban particles (PM2.5) collected in Houston, Texas. The cells were cultured for 11 days with the same person's blood lymphocytes and tetanus toxoid, and three lymphocyte signaling proteins were measured: interferon gamma, IL-4 and IL-13. Both asbestos types, at both concentrations, significantly raised interferon gamma. Only Libby amphibole significantly raised IL-4 and IL-13, which the authors said could reflect fewer subjects in the crocidolite groups (9 versus 13). PM2.5 significantly raised all three only at the higher concentration. Responses varied greatly between people, and a person's response to asbestos did not track their response to PM2.5. The authors concluded that the results support the hypothesis that such particles can alter macrophage antigen-presenting activity, producing an overactive immune response, and that this effect appeared nonspecific.

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 on human lung macrophages and blood lymphocytes (antigen-presenting cell assay)
• Who was studied: Alveolar macrophages obtained by lung lavage, plus blood lymphocytes, from normal, nonsmoking volunteers. 13 subjects for the Libby amphibole exposures and 9 for crocidolite; 11 for the lower and 12 for the higher PM2.5 concentration.
• Exposure: 24-hour exposure of macrophages to one of three particles. Crocidolite came from the Research Triangle Institute. Libby amphibole came from the EPA (Site no. 30 at the Libby, MT, vermiculite mine). The third was the water-insoluble fraction of PM2.5 collected over 6 months in Houston, TX. Each particle was used at two concentrations, printed as 25 or 50 mg/mL for each asbestos type and 50 or 100 mg/mL for PM2.5. Concentrations were limited by toxicity to the cells.
• Main results:
  • Interferon gamma: both forms of asbestos, at both concentrations, produced a significant increase compared with control.
  • IL-4 and IL-13: only Libby amphibole produced statistically significant changes. The authors said this could be related to the lower number of subjects in the crocidolite groups (9 compared to 13).
  • PM2.5: increases in interferon gamma, IL-4 and IL-13 were statistically significant only at the higher concentration.
  • An individual's responses to the two asbestos types were strongly and significantly correlated with each other. There were no significant positive correlations, and a slight nonsignificant negative correlation, between responses to asbestos and responses to PM2.5.
  • Individual subjects responded with extreme variability to particle stimulation.
  • IL-4 production was significantly correlated with interferon gamma production in cells exposed to Libby amphibole (.560), crocidolite (.817) and PM2.5 (.846), each at the higher concentration (Spearman rank correlation).
• The authors' conclusion: The authors concluded that their observations support the hypothesis that bioactive particles can alter macrophage antigen-presenting activity, producing an overactive immune response to nominal antigenic stimuli. They found that the immune modulation appeared nonspecific, with both TH1 and TH2 mediators up-regulated regardless of particle type. They also found between-subject variability in sensitivity to asbestos and PM2.5.
• Limitations the authors state:
  • A repeated-measures design would be needed to confirm true individual predispositions, but the invasive sampling limits repeated human sampling.
  • Fewer subjects in the crocidolite groups gave lower statistical power for that analysis.
  • Because the model was a coculture of macrophages and lymphocytes, it is questionable which cell type was responsible for the observed effect.
  • The PM2.5 used had not yet been characterized.

Mines named here

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

• Libby vermiculite mine, Montana

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Crocidolite, Libby amphiboles, Cytokine, Asbestos Exposure.

Related studies

• 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)
• Mobilization of iron from urban particulates leads to generation of reactive oxygen species in vitro and induction of ferritin synthesis in human lung epithelial cells — K.R. Smith, A.E. Aust (1997)
• Mechanisms associated with human alveolar macrophage stimulation by particulates — A. Holian, K. Kelley, et al. (1994)
• Human alveolar macrophage cytokine release in response to in vitro and in vivo asbestos exposure — R.C. Perkins, R.K. Scheule, et al. (1993)
• Asbestos and silica-induced changes in human alveolar macrophage phenotype — A. Holian, M.O. Uthman, et al. (1997)
• Asbestos induces apoptosis in human alveolar macrophages — R.F. Hamilton, L.L. Iyer, et al. (1996)

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