Pleural macrophage recruitment and activation in asbestos-induced pleural injury

Our plain-English summary of Pleural macrophage recruitment and activation in asbestos-induced pleural injury, by N. Choe, S. Tanaka, W. Xia, et al (Environmental Health Perspectives, 1997).

The study

• Authors: N. Choe, S. Tanaka, W. Xia, D.R. Hemenway, V.L. Roggli, E. Kagan
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1257-60
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury.

In plain English

The authors exposed three groups of male Fischer 344 rats by inhalation, 6 hours a day, 5 days a week, for 2 weeks. One group breathed NIEHS crocidolite asbestos (average 7.55 mg/m3), one NIEHS chrysotile asbestos (average 8.51 mg/m3), and one filtered room air. Rats were killed 1 and 6 weeks after exposure ended, and cells were washed from the pleural cavity, the space between the lungs' covering and the chest wall's lining. At 1 week, total pleural white cells were significantly higher in the crocidolite group than the air group. The chrysotile group showed a similar, not statistically significant, trend. At 6 weeks, both asbestos groups had significantly more than the air group. Pleural macrophages from both asbestos groups made significantly more TNF-alpha and nitric oxide than air-group macrophages at both times. Fibers were looked for only at 1 week. Crocidolite fibers, about 1 per 4000 cells, were found in one crocidolite-exposed rat; chrysotile-exposed rats were not examined. The authors concluded that inhaled fibers can reach the pleural space and that both fiber types can recruit and activate pleural macrophages.

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 inhalation experiment in rats comparing crocidolite-exposed, chrysotile-exposed and sham-exposed groups
• Who was studied: Three groups of male Fischer 344 rats, 47 days old and matched for size (mean group weights 149-151 g) before exposure. Pleural cell data are pooled from three rats per group at each time point (1 and 6 weeks after exposure ended).
• Exposure: Inhalation of NIEHS crocidolite asbestos (time-weighted average concentration 7.55 mg/m3) or NIEHS chrysotile asbestos (time-weighted average 8.51 mg/m3), or filtered room air for the sham group. Exposure lasted 6 hours a day, 5 days a week, for 2 weeks.
• Main results:
  • At 1 week after exposure ended, the total number of pleural white cells (leukocytes) was significantly greater in the crocidolite-exposed group than in the sham-exposed group (p less than 0.01). Table 1 gives 5.75 million cells for crocidolite versus 3.2 million for sham, as the pooled mean of three rats per group.
  • At 1 week, the chrysotile-exposed group showed a similar trend that was not statistically significant. Table 1 gives 4.83 million cells for chrysotile versus 3.2 million for sham.
  • At 6 weeks after exposure ended, total pleural white cells were still significantly greater than in the sham group after crocidolite (p less than 0.0005) and after chrysotile (p less than 0.05). Table 1 gives 13.14 million for crocidolite, 12.6 million for chrysotile and 8.82 million for sham.
  • All three groups, including the sham group, had more pleural white cells at 6 weeks than at 1 week. The authors described this as an age-related finding.
  • Pleural macrophage numbers rose after asbestos exposure, especially in the crocidolite group. In millions of cells (Table 1), the 1-week figures were 2.27 for sham, 4.08 for crocidolite and 3.67 for chrysotile. The 6-week figures were 6.21 for sham, 9.18 for crocidolite and 7.84 for chrysotile.
  • At 1 and 6 weeks, pleural macrophages from both the crocidolite-exposed and the chrysotile-exposed rats produced significantly more nitric oxide and TNF-alpha than macrophages from sham-exposed rats.
  • Fiber analysis was done only on rats killed at 1 week. No fibers were found in pleural lavage fluid from any exposed rat. In the pleural cell pellet of one of three crocidolite-exposed rats examined, crocidolite fibers were found at about 1 fiber per 4000 cells. These fibers were less than 0.5 micrometers wide and about 8 to 10 micrometers long. No fibers were found in sham-exposed rats, and chrysotile-exposed rats were not analyzed for fibers.
• The authors' conclusion: The authors concluded that inhaled asbestos fibers can translocate to the pleural space, and that inhaling either crocidolite or chrysotile can stimulate the recruitment and activation of pleural macrophages. They suggested the two fiber types may have a similar capacity to cause pleural space inflammation.
• Limitations the authors state:
  • The authors noted that the study looked only at TNF-alpha and nitric oxide, and that other cytokines and growth factors are likely also involved.
  • The authors reported that no fiber analysis was done on chrysotile-exposed rats.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Fibrosis, Standing, Amphibole Group, Serpentine Group, Crocidolite, Chrysotile, Scanning Electron Microscopy (SEM).

Related studies

• Pathogenesis of mesothelial reactions to asbestos fibers. Monocyte recruitment and macrophage activation — R.M. Branchaud, L.J. Garant, et al. (1993)
• How asbestos drives the tissue towards tumors: YAP activation, macrophage and mesothelial precursor recruitment, RNA editing, and somatic mutations — H. Rehrauer, L. Wu, et al. (2018)
• Cytotoxic effect of asbestos on macrophages in different activation states — A. Wright, K. Donaldson, et al. (1983)
• Asbestos exposure upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1 — N. Choe, J. Zhang, et al. (1999)
• Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress — W.A. Swain, K.J. O'Byrne, et al. (2004)
• 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)

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