Asbestos exposure upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1

Our plain-English summary of Asbestos exposure upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1, by N. Choe, J. Zhang, A. Iwagaki, et al (The American Journal of Physiology, 1999).

The study

• Authors: N. Choe, J. Zhang, A. Iwagaki, S. Tanaka, D.R. Hemenway, E. Kagan
• Journal: The American Journal of Physiology
• Published: 1999;277(2):L292-300
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study was designed to assess the effects of in vitro and in vivo asbestos exposure on the adhesion of rat pleural leukocytes (RPLs) labeled with the fluorochrome calcein AM to rat pleural mesothelial cells (RPMCs). Exposure of RPMCs for 24 h to either crocidolite or chrysotile fibers (1.25-10 microgram/cm(2)) increased the adhesion of RPLs to RPMCs in a dose-dependent fashion, an effect that was potentiated by interleukin-1beta. These findings were not observed with nonfibrogenic carbonyl iron particles. Crocidolite and chrysotile plus interleukin-1beta also upregulated vascular cell adhesion molecule-1 mRNA and protein expression in RPMCs, and the binding of RPL to asbestos-treated RPMCs was abrogated by anti-vascular cell adhesion molecule-1 antibody. PRLs exposed by intermittent inhalation to crocidolite for 2 wk manifested significantly greater binding to RPMCs than did RPLs from sham-exposed animals. The ability of asbestos fibers to upregulate RPL adhesion to RPMCs may play a role in the induction and/or potentiation of asbestos-induced pleural injury.

In plain English

This laboratory study used rat cells and rats. It asked whether asbestos makes rat pleural leukocytes (white blood cells from the chest cavity) stick more to rat pleural mesothelial cells (the cells lining the pleura). In cultured mesothelial cells, crocidolite and chrysotile fibers (1.25 to 10 µg/cm2 for 24 hours) increased leukocyte adhesion in a dose-dependent way. Nonfibrogenic carbonyl iron particles also increased adhesion, but with no dose-response, and fibers at 5 to 10 µg/cm2 caused significantly more adhesion than carbonyl iron. With interleukin-1 beta, an inflammatory signal, added to asbestos, the authors reported adhesion rose by about 118% for crocidolite and 134% for chrysotile. Asbestos boosted the interleukin-1 beta increase in the adhesion protein VCAM-1. An antibody against VCAM-1 reduced adhesion; one against ICAM-1 did not. Leukocytes from rats that inhaled crocidolite for two weeks adhered more than those from sham-exposed rats. The authors said they could not settle whether the fiber types differ, because fiber mass does not show fiber number. They concluded that increased adhesion may play a role in asbestos-induced pleural injury.

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 study with cultured rat pleural mesothelial cells (in vitro), plus an animal inhalation experiment (in vivo)
• Who was studied: Fischer 344 rats. Mesothelial cells were grown from unexposed rats. Two groups of male Fischer 344 rats (41 days old) were exposed by inhalation to crocidolite or to filtered room air (sham). The adhesion experiments with inhalation-exposed rats used 3 rats per group.
• Exposure: In vitro: crocidolite and chrysotile fibers from the National Institute of Environmental Health Sciences at 1.25 to 10.0 µg/cm2, compared with nonfibrogenic carbonyl iron particles, with or without interleukin-1 beta (20 ng/ml) or tumor necrosis factor-alpha (10 ng/ml). In vivo: UICC crocidolite inhaled 6 hours a day, 5 days a week, for 2 weeks, at a time-weighted concentration of 10.52 plus or minus 2.31 (SE) mg/m3. Rats were killed 10 days after exposure ended.
• Main results:
  • In cultured mesothelial cells, crocidolite and chrysotile at 5 to 10 µg/cm2 caused significantly greater leukocyte adhesion than carbonyl iron.
  • Carbonyl iron also increased adhesion, but showed no dose-response relationship.
  • When interleukin-1 beta was added to asbestos-containing cultures, adhesion was increased by about 118% with crocidolite and about 134% with chrysotile.
  • Interleukin-1 beta raised VCAM-1 protein on mesothelial cells by about 357%, and either fiber type potentiated this. Asbestos alone did not significantly change protein levels.
  • Asbestos fibers or interleukin-1 beta caused an early rise in VCAM-1 mRNA at 2 hours that peaked at 8 hours.
  • In cultures given interleukin-1 beta plus asbestos, an anti-VCAM-1 antibody significantly reduced adhesion. Asbestos did not raise ICAM-1 expression, and an anti-ICAM-1 antibody did not reduce adhesion.
  • Pleural leukocytes from crocidolite-exposed rats showed significantly greater adhesion than those from sham-exposed rats. This held for unstimulated mesothelial cells and for cells stimulated with crocidolite or interleukin-1 beta (3 rats per group).
  • Pleural leukocytes were mostly macrophages: about 74.8% in unexposed rats (10 rats) and 74.0% in crocidolite-exposed rats (3 rats). The authors reported no significant difference in cell composition between the groups.
  • Aminoguanidine, a nitric oxide synthesis blocker, significantly increased adhesion to unstimulated and asbestos-stimulated mesothelial cells. It had no noticeable effect when cells were stimulated with interleukin-1 beta plus asbestos. The authors suggested nitric oxide played only a minor role in that setting.
• The authors' conclusion: The authors concluded that in vitro and in vivo asbestos exposure increased adhesion of pleural leukocytes to pleural mesothelial cells. They found VCAM-1, but not ICAM-1, important to this binding. They suggested that increased leukocyte adhesiveness may play a role in initiating or potentiating asbestos-induced injury to the pleural mesothelium.
• Limitations the authors state:
  • Chrysotile appeared to have a greater effect than crocidolite by mass. The authors said this was inconclusive because mass measurements do not show actual fiber numbers.
  • The study did not examine how asbestos fibers increased VCAM-1 expression.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Mesothelial Cells, Crocidolite, Chrysotile.

Related studies

• Asbestos fibers and interleukin-1 upregulate the formation of reactive nitrogen species in rat pleural mesothelial cells — N. Choe, S. Tanaka, et al. (1998)
• Pulmonary and pleural leukocytes from F344 rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers — T.R. Gelzleichter, J.B. Mangum, et al. (1996)
• Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells — S. Tanaka, N. Choe, et al. (2000)
• Increased production of plasminogen activator inhibitor in vitro by pleural leukocytes from rats intratracheally instilled with crocidolite asbestos — X.Y. Li, G.M. Brown, et al. (1991)
• Intratracheal injection of crocidolite asbestos depresses the secretion of tumor necrosis factor by pleural leukocytes in vitro — X.Y. Li, D. Lamb, et al. (1992)
• Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos — G.D. Hill, J.B. Mangum, et al. (2003)

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