Macrophage stimulation and the inflammatory response to asbestos

Our plain-English summary of Macrophage stimulation and the inflammatory response to asbestos, by J.A. Hamilton (Environmental Health Perspectives, 1980).

The study

• Author: J.A. Hamilton
• Journal: Environmental Health Perspectives
• Published: 1980;34:69-74
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chrysotile fibers injected into the peritoneal cavity of mice elicit a cellular exudate. Macrophages appearing in this exudate produce high levels of the neutral protease, plasminogen activator, when compared with the resident peritoneal macrophage population. In contrast, the levels of lysozyme and two lysosomal enzymes are the same for the two macrophage types. The asbestos-induced macrophages producing the plasminogen activator appear to have descended from recently divided precursors. Low concentrations of anti-inflammatory glucocorticoids inhibit macrophage plasminogen activator synthesis. Preliminary experiments indicate that different asbestos types induce hyperemia in skin, and also shorten the partial thromboplastin time of plasma and generate the release of kinins. These observations could be interrelated and are suggested as representing some aspects of the inflammatory response of the host to asbestos exposure.

In plain English

This laboratory study, mainly in mice, examined how chrysotile asbestos (UICC Chrysotile Type B) affects macrophages, a type of immune cell, and other parts of the inflammatory response. Mice received asbestos or other irritants injected into the peritoneal (abdominal) cavity, and cells were collected 4 days later. Cells from asbestos-injected mice broke down fibrin far more than cells from controls. At 24 hours, they released 52.9% of the radioactive label after a 500 microgram asbestos dose, compared with 1.4% for saline-injected mice, 3.0% for latex particles and 4.9% for endotoxin. In a labeling test, 72 plus or minus 4% of asbestos-induced macrophages carried a DNA marker, against 11 plus or minus 1% in controls. The author took this to suggest the active cells came from recently divided precursors. The steroid dexamethasone cut plasminogen activator secretion by asbestos-primed macrophages from 960 to 24 units per mg cell protein. Briefly described preliminary work indicated that asbestos fibers increased blood flow in rabbit skin and shortened the partial thromboplastin time, a clotting test, of normal human plasma. The author suggested the data were relevant to early inflammatory events after asbestos exposure and said lung macrophages should also be tested.

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 and cell-culture laboratory experiments (mouse peritoneal macrophages), with brief mention of preliminary rabbit skin and human plasma experiments
• Who was studied: Peritoneal cells from NCS (Rockefeller) mice or BDF mice, 8-12 weeks old. Four mice were used for the DNA-labeling experiment. Preliminary experiments used rabbit skin and normal human plasma.
• Exposure: UICC Chrysotile Type B injected into the peritoneal cavity at doses from 1 to 300 micrograms, plus 100, 300 and 500 microgram doses in specific experiments. Comparison groups received thioglycollate, latex, endotoxin, or saline/PBS. In rabbit skin, six asbestos fibers including chrysotiles and amphiboles were tested.
• Main results:
  • Percentage of radioactivity released from fibrin at 24 hours by 2 x 10^6 peritoneal cells. Asbestos (500 micrograms): 52.9%. Unstimulated (PBS): 1.4%. Latex (500 micrograms): 3.0%. Endotoxin (30 micrograms): 4.9%.
  • Percentage of macrophages labeled with tritiated thymidine (means of triplicate cultures with standard errors). Unstimulated: 11 plus or minus 1. Thioglycollate: 69 plus or minus 6. Asbestos: 72 plus or minus 4.
  • The author concluded it appears likely that the macrophages secreting plasminogen activator descended from recently divided precursors.
  • Secreted plasminogen activator from macrophages of mice primed with 100 micrograms asbestos was 960 units/mg cell protein. With 10 to the minus 7 molar dexamethasone added in vitro, it was 24 units/mg cell protein.
  • Preliminary experiments indicated that asbestos fibers increase blood flow at injection sites in the skin and shorten the partial thromboplastin time of normal human plasma.
• The authors' conclusion: The author suggested that the data presented are relevant to some early vascular events associated with asbestos exposure and to the role of inflammatory macrophages responding to asbestos. The author proposed that plasmin-mediated tissue destruction might be part of the granulomatous response to asbestos.
• Limitations the authors state:
  • The mouse peritoneal macrophage is a model system. The author said lung macrophages, which are more likely to contact asbestos, should also be tested.
  • How asbestos fibers interact with macrophages is unknown.
  • The author said plasminogen activator stimulation is not claimed to be the only critical event in asbestos lesions.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Chrysotile, Peritoneal Cavity, Exudate, Asbestos Exposure.

Related studies

• Degradation of cartilage proteoglycan and collagen by synovial cells. Stimulation by macrophages under activation by phagocytosis, lymphocyte factors, bacterial products or other inflammatory stimuli — C. Peeters-Joris, G. Vaes (1984)
• Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids — J. Hamilton, J.D. Vassalli, et al. (1976)
• Effects of sustained stimulation with multi-wall carbon nanotubes on immune and inflammatory responses in mice — A. Yamaguchi, T. Fujitani, et al. (2012)
• Lysosomal enzyme secretion by macrophages during intracellular storage of particles — R.T. Dean, W. Hylton, et al. (1979)
• The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells — F.A. Murphy, A. Schinwald, et al. (2012)
• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation — H.U. Schorlemmer, P. Davies, et al. (1977)

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