Induction of macrophage plasminogen activator by asbestos is independent of PKC activation

Our plain-English summary of Induction of macrophage plasminogen activator by asbestos is independent of PKC activation, by D. Lison, F. Raguzzi, R. Lauwerys (Archives of Toxicology, 1991).

The study

• Authors: D. Lison, F. Raguzzi, R. Lauwerys
• Journal: Archives of Toxicology
• Published: 1991;65(5):386-9
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study was undertaken to assess whether plasminogen activator (PA) induction in macrophages exposed to chrysotile fibers is mediated by protein kinase C (PKC) activation. In PKC depleted J774 cells, PA induction could be elicited by chrysotile whereas, as expected, the response to phorbol myristate acetate (PMA) was abolished. The effect of PMA and chrysotile on the distribution of PKC activity in the J774 cell line was also compared by measuring the enzyme catalytic activity and phorbol dibutyrate (PDBu) binding sites. No redistribution of PKC was observed after stimulation with PA inducing doses of chrysotile, whereas a clear translocation was observed with PMA. It is concluded that the mechanism of PA induction by chrysotile in this macrophage-like cell line is independent of PKC activation.

In plain English

This was a laboratory study of a mouse cell line (J774) of macrophage-like cells, a type of immune cell. It was carried out at the Catholic University of Louvain in Brussels. The authors asked whether chrysotile asbestos raises these cells' plasminogen activator activity by switching on an enzyme called protein kinase C. Plasminogen activator is an inflammatory mediator. They compared chrysotile with PMA, a chemical known to act through this enzyme. A drug called auranofin almost completely blocked the response to both, but the authors noted that it is not a specific blocker of the enzyme. In cells first depleted of the enzyme by long PMA treatment, PMA no longer significantly changed plasminogen activator activity. Chrysotile still raised it, to 125% of control (p less than 0.05). PMA raised the enzyme's activity in the cell membranes to up to 300% of the control value. Chrysotile changed neither cytosolic nor membrane activity, and phorbol dibutyrate binding showed no statistically significant change after chrysotile. The authors concluded that in this cell line, chrysotile induces plasminogen activator independently of protein kinase C activation.

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 (in vitro) experiment on a cultured macrophage-like cell line
• Who was studied: Murine (mouse) monocyte-macrophage J774 cell line, grown in culture at the Industrial Toxicology and Occupational Medicine Unit, Catholic University of Louvain, Brussels
• Exposure: Chrysotile fibers (UICC standards) at 150 micrograms per million cells, compared with phorbol myristate acetate (PMA, 0.1 micromolar) and saline controls; some cells were pretreated with auranofin or depleted of protein kinase C by 18 hours of PMA
• Main results:
  • Pretreatment with auranofin (10 micromolar, 15 min) almost completely prevented plasminogen activator induction by both chrysotile and PMA. It did not significantly affect activity in unstimulated cells (20 plus or minus 1.6 and 22 plus or minus 3.2 nmol pNA/h2/well without and with auranofin).
  • In PMA-pretreated (protein kinase C depleted) cells, PMA did not significantly modify plasminogen activator activity, while chrysotile still induced it, to 125 plus or minus 2.3% of control activity (p less than 0.05)
  • After 30 minutes of PMA exposure, membrane protein kinase C activity increased to up to 300% of the control value. After chrysotile exposure, neither cytosolic nor membrane activity changed compared with control cells.
  • No statistically significant change in phorbol dibutyrate (PDBu) binding sites in the cytosol or membrane fractions was observed after chrysotile stimulation
• The authors' conclusion: The authors concluded that the mechanism of plasminogen activator induction by chrysotile in macrophage-like J774 cells is independent of protein kinase C activation
• Limitations the authors state:
  • Auranofin, which blocked the response to both chrysotile and PMA, binds various sulfhydryl-rich proteins and is not a specific protein kinase C inhibitor
  • The response to chrysotile in the enzyme-depleted experiments (125% of control) was lower than in untreated cells (about 200% of control). The authors suggested this might be due to the 18-hour serum-free incubation.

Topics

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

Related studies

• Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids — J. Hamilton, J.D. Vassalli, et al. (1976)
• 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)
• Suppression of the neutral protease activity of macrophages treated with asbestos in vitro — J.A. Hamilton (1983)
• Activation of protein kinase C by crocidolite asbestos in hamster tracheal epithelial cells — M. Perderiset, J.P. Marsh, et al. (1991)
• 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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