Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos

Our plain-English summary of Soluble ICAM-1, MCP-1, and MIP-2 protein secretion by rat pleural mesothelial cells following exposure to amosite asbestos, by G.D. Hill, J.B. Mangum, O.R. Moss, et al (Experimental Lung Research, 2003).

The study

• Authors: G.D. Hill, J.B. Mangum, O.R. Moss, J.I. Everitt
• Journal: Experimental Lung Research
• Published: 2003;29(5):277-90
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Pleural inflammation is a sequela of exposure to toxic mineral fibers such as amosite asbestos. This inflammatory response involves the influx of leukocytes from the vasculature into the pleural space. Adhesion molecules such as intercellular adhesion molecule-1 (ICAM)-1 and chemokines such as monocyte chemoattractant protein-1 (MCP)-1 and macrophage inhibitory protein-2 (MIP)-2 are known to be important in pulmonary inflammation following inhalation of particulate matter. However, little is known about their role in pleural inflammation secondary to amosite asbestos exposure. Because the pleural mesothelial cell is believed to be a key target cell of asbestos exposure, the purpose of this study was to determine if ICAM-1, MCP-1, and MIP-2 proteins were secreted by these mesothelial cells following in vitro and in vivo exposure to amosite asbestos. Increased levels of ICAM-1 and MCP-1 protein were measured following 24 or 48 hours exposure of cultured rat pleural mesothelial cells to amosite fibers (1.5 to 5.0 micro g/cm(2)). Increased levels of ICAM-1, MCP-1, and MIP-2 protein were found in pleural lavage fluid from Fischer-344 rats exposed to amosite asbestos for 4 and 12 weeks and after a 12-week recovery period (following the 12-week exposure period). These findings suggest that the secretion of ICAM-1, MCP-1, and MIP-2 by rat pleural mesothelial cells may contribute to amosite-induced pleural inflammation.

In plain English

This laboratory study asked whether rat pleural mesothelial cells, lining the chest cavity, release three inflammation-related proteins (ICAM-1, MCP-1, MIP-2) after amosite asbestos exposure. Cultured cells were treated for 24 or 48 hours with amosite at doses printed as 1.5 or 5.0 mg/cm2, or with grunerite, a non-fibrous mineral chemically identical to amosite, at 5.0 mg/cm2. The scan seems to drop micro symbols, so the unit is uncertain. Compared with untreated cells, ICAM-1 was significantly higher after 48 hours at the lower amosite dose, and MCP-1 after 24 hours at the higher dose. MIP-2 rose with dose, but not significantly. Male Fischer-344 rats (6 per group) inhaled amosite or filtered air for 4 or 12 weeks, at levels the authors noted were several orders of magnitude above current regulatory guidelines. In fluid washed from the chest cavity, all three proteins were significantly higher than in controls after 12 weeks of amosite, and MCP-1 also after a further 12-week recovery. The authors concluded these mesothelial-cell proteins may be important in pleural inflammation, including that linked to mineral fibers.

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 experiment combining cultured rat pleural mesothelial cells (in vitro) with an inhalation study in rats (in vivo)
• Who was studied: A rat pleural mesothelial cell line (SFM-1 cells, from parietal pleura), with three plates per treatment. Also male Fischer-344 rats, about 13 weeks old and weighing 250 to 275 g, 6 per group, exposed to amosite or filtered air.
• Exposure: In culture, cells received UICC amosite at 1.5 or 5.0 mg/cm2 or non-fibrous grunerite at 5.0 mg/cm2 for 24 or 48 hours. These are the units as printed in the scanned text; the mass unit may have lost a micro symbol in scanning. In rats, exposure was nose-only inhalation of amosite or filtered air, 4 hours/day, 5 days/week, for up to 12 weeks. The amosite target was 750 fibers/cc. The measured average was 1204 fibers/cc of all lengths, of which about 843 fibers/cc were WHO fibers. Rats were examined at 4 and 12 weeks, and one 12-week group was examined after a further 12-week recovery period.
• Main results:
  • Cultured cells: ICAM-1 was significantly higher than in control cells after 48 hours of treatment with the lower amosite concentration (1.5). The authors noted the response was not dose-dependent.
  • Cultured cells: MCP-1 was significantly increased after 24 hours of treatment with the higher amosite concentration (5.0).
  • Cultured cells: MIP-2 showed a dose-dependent increase with amosite, but this increase was not statistically significant.
  • Rats: ICAM-1 in pleural lavage fluid was higher in amosite-exposed rats than in controls. The increase was significant at 12 weeks of exposure.
  • Rats: MCP-1 in pleural lavage fluid was significantly increased after 12 weeks of amosite exposure and after the 12-week recovery period.
  • Rats: MIP-2 in pleural lavage fluid was significantly higher than in controls after 12 weeks of amosite exposure.
  • Rats (reported in the Discussion): white blood cells entering the pleural cavity increased by 64% after 4 weeks and by 165% after 12 weeks of amosite exposure. Neutrophil counts rose 10-fold at 12 weeks.
• The authors' conclusion: The authors concluded that ICAM-1, MCP-1 and MIP-2 coming from pleural mesothelial cells may be important in mediating pleural inflammation, including inflammation associated with mineral fiber exposure.
• Limitations the authors state:
  • The authors stated that the inhaled asbestos exposure was several orders of magnitude higher than current regulatory guidelines.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Amosite, Inflammation, Sequela, Mineral Fiber, Macrophage, Asbestos Exposure.

Related studies

• Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells — S. Tanaka, N. Choe, et al. (2000)
• 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 upregulates the adhesion of pleural leukocytes to pleural mesothelial cells via VCAM-1 — N. Choe, J. Zhang, et al. (1999)
• Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2011)
• The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results — D.M. Bernstein, R.A. Rogers, et al. (2010)
• Mesothelial cells activate the plasma kallikrein-kinin system during pleural inflammation — J.F. Varano Della Vergiliana, S. Lansley, et al. (2011)

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