Pathogenesis of mesothelial reactions to asbestos fibers. Monocyte recruitment and macrophage activation

Our plain-English summary of Pathogenesis of mesothelial reactions to asbestos fibers. Monocyte recruitment and macrophage activation, by R.M. Branchaud, L.J. Garant, A.B. Kane (Pathobiology, 1993).

The study

• Authors: R.M. Branchaud, L.J. Garant, A.B. Kane
• Journal: Pathobiology
• Published: 1993;61(3-4):154-63
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure to asbestos fibers leads to a variety of mesothelial reactions: pleural effusions, fibrotic pleural plaques, and malignant mesotheliomas. An animal model was developed to reproduce these lesions in C57B1/6 mice using weekly intraperitoneal injections of asbestos fibers. After exposure to asbestos fibers, monocytes were recruited into the abdominal cavity and acquired the characteristics of inflammatory or nonspecifically activated macrophages. Nontoxic titanium dioxide or toxic silica particles did not produce activation of the free peritoneal macrophage population. Aggregates of asbestos fibers were found on the diaphragm and other peritoneal surfaces within only 24 h after a single injection. Macrophage recruitment to these sites peaked between 3 and 5 days, while activated macrophages persisted up to 14 days. Recruitment and activation of macrophages by repeated exposures to asbestos fibers may contribute to chronic damage of the mesothelial lining caused by these mineral fibers.

In plain English

This was an animal experiment. Male C57Bl/6 mice were injected in the abdominal (peritoneal) cavity with 100 micrograms of crocidolite asbestos, quartz (silica) or titanium dioxide, either once or weekly for up to 42 weeks. They were compared with mice given saline or thioglycollate broth, an irritant. Asbestos or thioglycollate yielded almost tenfold more peritoneal cells than saline, silica, titanium dioxide or no injection. Three days after one crocidolite injection, 40-50% of peritoneal cells ingested coated red blood cells, and 80-90% bound a lectin that marks activated macrophages. The lectin figures were 19% after titanium dioxide and 39% after silica. Between 1 and 4 days after asbestos, 20-55% of cells showed a marker of newly recruited monocytes, against 1-2% three days after titanium dioxide or silica. Repeated asbestos injections produced growing nodules of fibers and macrophages on the peritoneal lining. Activated macrophages persisted there. After 42 weekly injections, titanium dioxide left a normal lining, while silica slightly thickened it by fibrosis. The authors concluded that repeated asbestos exposure may contribute to chronic damage of the mesothelial lining by recruiting and activating 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 experiment: a mouse model using single or repeated weekly injections of mineral particles into the peritoneal cavity
• Who was studied: Male C57Bl/6 mice aged 6 to 20 weeks; at least 2 mice per time point and treatment (2-3 animals per value in the cell-yield table)
• Exposure: Single or repeated weekly intraperitoneal injections of 100 micrograms of crocidolite asbestos, quartz (silica) or titanium dioxide. Controls received saline (PBS) or 1.5 ml thioglycollate broth. Mice were examined 4 hours to 21 days after a single injection, or after 4 to 42 weeks of weekly injections.
• Main results:
  • Mice injected with asbestos or thioglycollate yielded almost tenfold more peritoneal cells than uninjected, saline-, silica- or titanium dioxide-injected mice.
  • Three days after a single crocidolite injection, 40-50% of peritoneal cells ingested one or more complement-coated sheep red blood cells.
  • After 3 days of asbestos exposure, 80-90% of cells bound G. simplicifolia lectin.
  • The percentage of cells binding the lectin was 19% after titanium dioxide and 39% after silica.
  • Between 1 and 4 days after asbestos injection, 20-55% of cells had peroxidase activity, a marker of newly recruited monocytes.
  • Three days after titanium dioxide or silica injection, only 1-2% of peritoneal cells had peroxidase activity.
  • Only 3.5% of macrophages harvested 3 days after crocidolite injection took up thymidine, compared with 4.5% of resident macrophages. The authors took this to mean the increase in macrophages was unlikely to come from cell division.
  • With repeated weekly asbestos injections, peritoneal nodules became progressively larger and visible to the naked eye.
  • The nodules protruded from the peritoneal surface and were covered by mesothelial cells.
  • Starting 12 hours after a single crocidolite injection, about 25% of macrophages gathered around asbestos fiber clusters had strong acid phosphatase activity.
  • Activated macrophages persisted at these sites for up to 14 days. In contrast, activated macrophages disappeared from the free peritoneal cell population between 7 and 14 days.
  • After 42 weekly injections of titanium dioxide, the peritoneal lining was normal.
  • After 42 weekly injections of silica, the parietal peritoneal lining was slightly thickened by fibrosis, with no nodules.
• The authors' conclusion: The authors concluded that recruitment and activation of macrophages by repeated exposures to asbestos fibers may contribute to chronic damage of the mesothelial lining caused by mineral fibers.
• Limitations the authors state:
  • The authors noted that the substances responsible for drawing in and activating monocytes after asbestos exposure in the living animal were unknown.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Pleural Effusion, Pleural Plaques, Malignant Mesothelioma, Diaphragm, Mineral Fiber.

Related studies

• Pleural macrophage recruitment and activation in asbestos-induced pleural injury — N. Choe, S. Tanaka, et al. (1997)
• Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts — P. Nyberg, M. Klockars (1990)
• Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages — A.L. Chéné, S. d'Almeida, et al. (2016)
• 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)
• Pulmonary reaction to long and short asbestos fibers is independent of fibroblast growth factor production by alveolar macrophages — I.Y. Adamson, D.H. Bowden (1990)

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