Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids

Our plain-English summary of Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids, by J. Hamilton, J.D. Vassalli, E. Reich (The Journal of Experimental Medicine, 1976).

The study

• Authors: J. Hamilton, J.D. Vassalli, E. Reich
• Journal: The Journal of Experimental Medicine
• Published: 1976;144(6):1689-94
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Intraperitoneal injection of asbestos fibres into mice induces the formation of exudates containing macrophages that produce plasminogen activator. Like-wise, in vitro addition of asbestos to macrophage cultures stimulates plasminogen activator secretion; the synthesis and secretion of lysozyme and lysosomal enzymes are not changed under these conditions. The enhanced secretion of plasminogen activator by macrophages exposed to asbestos is suppressed by low concentrations of anti-inflammatory steroids.

In plain English

This laboratory study looked at how mouse immune cells called macrophages respond to chrysotile asbestos (U.I.C.C. Chrysotile "B", Canadian sample). Mice were injected in the abdominal (peritoneal) cavity with asbestos or with comparison materials (saline, latex particles, thioglycollate or endotoxin), and cells were collected 4 days later. Asbestos raised the number of abdominal cells to 9 to 20 million; latex caused only minor changes. Macrophages from asbestos-injected mice secreted at least 20-fold more of an enzyme called plasminogen activator than macrophages from saline-injected mice. Their secretion of lysozyme and two lysosomal enzymes did not change. Adding asbestos to cultured macrophages from endotoxin-injected mice for 2 hours raised fibrinolytic activity, a measure of this enzyme, two to fivefold for at least 4 days. The steroid dexamethasone blocked more than 95% of the asbestos-induced enzyme production. The study used mouse abdominal cells, not lung cells or people. The authors suggested that anti-inflammatory steroids may be of value in controlling the chronic inflammation associated with asbestosis.

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 experiment (mice injected with asbestos, and mouse macrophages exposed to asbestos in culture)
• Who was studied: NCS mice (25-30 g) from The Rockefeller University, New York, and peritoneal (abdominal) cells taken from them; the number of mice is not stated
• Exposure: U.I.C.C. Chrysotile "B" asbestos (Canadian sample). Injected into the peritoneal cavity at doses from 1 to 300 micrograms, or added to cultured macrophages at 1 to 100 micrograms for 2 hours (in some experiments 24 hours). Comparisons were saline (PBS), latex particles, thioglycollate medium and endotoxin.
• Main results:
  • In injected mice, asbestos increased the number of peritoneal cells to 9 to 20 million, rising with dose from 10 to 100 micrograms. Latex caused only minor changes in the cell population.
  • After injection of 100 micrograms of asbestos, 70% of macrophage nuclei were labelled with tritiated thymidine during the 4-day period, a sign of recently divided cells.
  • In macrophages from asbestos-injected mice, plasminogen activator secretion was at least 20-fold higher than in macrophages from saline (PBS)-injected controls.
  • Macrophages from asbestos-injected mice and from saline-injected controls secreted the same amounts of lysozyme. No difference was seen in the two lysosomal enzymes.
  • In macrophages from asbestos-injected mice, dexamethasone inhibited plasminogen activator production by more than 95% (at 10 to the minus 7 molar).
  • In cultured macrophages from endotoxin-injected mice, 2 hours of exposure to 1 to 100 micrograms of asbestos produced a two to fivefold increase in fibrinolytic activity that persisted for at least 4 days.
  • In these cultured endotoxin-primed macrophages, asbestos had no effect on secretion of lysozyme or of two lysosomal enzymes.
  • In cultured endotoxin-primed macrophages, the asbestos effect on plasminogen activator secretion was inhibited more than 95% by dexamethasone and more than 90% by colchicine. Among the steroids tested, the order of potency was dexamethasone, then fluorocortisone, prednisolone, hydrocortisone and corticosterone.
• The authors' conclusion: The authors concluded that their findings suggest a specific role for plasminogen activator in inflammation. They suggested that anti-inflammatory steroids may be of value in controlling the chronic inflammation associated with asbestosis.
• Limitations the authors state:
  • Asbestos fiber sizes varied and uptake of asbestos by the cells was not measured, so a link between the cells engulfing asbestos and the increased enzyme secretion could not be proven.
  • The mechanism by which asbestos produced the inflammatory exudate was not known.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Exudate.

Related studies

• Induction of macrophage plasminogen activator by asbestos is independent of PKC activation — D. Lison, F. Raguzzi, et al. (1991)
• Suppression of the neutral protease activity of macrophages treated with asbestos in vitro — J.A. Hamilton (1983)
• Macrophage stimulation and the inflammatory response to asbestos — J.A. Hamilton (1980)
• Increased alveolar plasminogen activator in early asbestosis — A. Cantin, C. Allard, et al. (1989)
• Expression of plasminogen activator and plasminogen activator inhibitor by rat mesothelioma induced by asbestos — S.P. Lenz, F.H. Green, et al. (1993)
• Asbestos upregulates expression of the urokinase-type plasminogen activator receptor on mesothelial cells — R.C. Perkins, V.C. Broaddus, et al. (1999)

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