Suppression of the neutral protease activity of macrophages treated with asbestos in vitro

Our plain-English summary of Suppression of the neutral protease activity of macrophages treated with asbestos in vitro, by J.A. Hamilton (Environmental Health Perspectives, 1983).

The study

• Author: J.A. Hamilton
• Journal: Environmental Health Perspectives
• Published: 1983;51:103-8
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Macrophages are often conspicuous in asbestos-induced inflammatory lesions. Chrysotile type B elicits macrophages into the peritoneal cavity of mice which produce high levels of the neutral protease, plasminogen activator; in vitro addition of these same fibers to mouse peritoneal macrophages stimulates enzyme production. It is reported here that, for endotoxin-elicited mouse peritoneal macrophages fed chrysotile type B in vitro, the increased plasminogen activator activity is suppressed by low concentrations of anti-inflammatory steroids. Other active drugs include colchicine and vinblastine. These studies are considered important, as they suggest an approach to controlling the levels of a potentially deleterious enzyme system (PA-plasmin) from macrophages treated with asbestos fibers.

In plain English

This was a laboratory study by a single author, done on mouse cells in culture dishes, not on people. Immune cells called macrophages were collected from the abdominal cavity of mice injected four days earlier with endotoxin (a bacterial product) or with salt solution. The cells were fed IARC chrysotile type B asbestos, or latex beads for comparison. The author then measured plasminogen activator, an enzyme that breaks down protein. Asbestos raised this enzyme's activity in both groups of cells. In one experiment, fibrin breakdown by endotoxin-primed cells rose from 8% to 34% with 100 micrograms of asbestos. Adding the steroid drugs dexamethasone or prednisolone cut this to 1% and 2%, while progesterone gave 26%. Dexamethasone was effective at concentrations as low as 10 to the minus 9 molar. Colchicine reduced the enzyme released into the culture fluid. Asbestos did not change the secretion of lysozyme or two lysosomal enzymes. The author concluded the findings suggest an approach to controlling a potentially harmful enzyme system. The author cautioned that it was not established that fiber uptake caused the increase.

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 mouse cells in culture
• Who was studied: Peritoneal (abdominal cavity) macrophages from NCS (Rockefeller) mice weighing 25-30 g or BDF mice aged 8-12 weeks. The mice had been injected 4 days earlier with phosphate-buffered saline (control) or 30 micrograms of endotoxin. The work was done at Memorial Sloan-Kettering Cancer Center, New York.
• Exposure: IARC chrysotile type B asbestos, added to cultured cells in amounts from 0.1 to 100 micrograms, with latex particles as a comparison particle. The asbestos was a gift from Johns-Manville Corp.
• Main results:
  • Asbestos increased plasminogen activator activity of macrophages from endotoxin-injected mice and from saline-injected control mice. The control cells showed a longer lag period. As little as 0.1 micrograms of fiber raised activity in endotoxin-primed cells.
  • For endotoxin-primed cells, radioactivity released at 24 hr was 8%. For endotoxin-primed cells given 100 micrograms of asbestos it was 34%. At 10 to the minus 7 molar, dexamethasone reduced the asbestos value to 1%, prednisolone to 2%, and progesterone to 26%. The inhibition persisted for at least 72 hr.
  • In a second experiment, asbestos-treated endotoxin-primed cells released 59% of radioactivity. With hydrocortisone this was 21%, with 9-fluorocortisone 25%, and with desoxycorticosterone 32%. Aldosterone gave 45%, testosterone 56%, and estradiol 56%. Colchicine (51%) and vinblastine (41%) had little influence in this fibrin-plate test.
  • Dexamethasone was effective even at 10 to the minus 9 molar. At that dose, asbestos-treated cells released 12% of radioactivity, compared with 34% without the drug.
  • Endotoxin-primed cells secreted 620 plasminogen activator units per mg cell protein. Cells also given 100 micrograms of asbestos secreted 2380 units. With dexamethasone, asbestos-treated cells secreted 110 units, and with colchicine 210 units.
  • Asbestos (or latex) had no effect on secretion of lysozyme or of two lysosomal enzymes, N-acetyl-glucosaminidase and galactosidase. Dexamethasone and colchicine also did not alter these enzymes.
• The authors' conclusion: The author concluded that the asbestos-stimulated enzyme activity is suppressed by anti-inflammatory glucocorticoids. The author considered that this suggests an approach to controlling the levels of a potentially deleterious enzyme system (PA-plasmin) from macrophages treated with asbestos.
• Limitations the authors state:
  • The author stated it is unwarranted to conclude that uptake (phagocytosis) of fibers causes the increased enzyme activity until fiber uptake is measured quantitatively.
  • The author framed the harmful role of excess enzyme activity around asbestos-exposed macrophages as an assumption.

Topics

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

Related studies

• Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids — J. Hamilton, J.D. Vassalli, et al. (1976)
• Induction of macrophage plasminogen activator by asbestos is independent of PKC activation — D. Lison, F. Raguzzi, et al. (1991)
• In vitro reactivity of alveolar macrophages and red blood cells with asbestos fibres treated with oxalic acid, sulfur dioxide and benzo-3,4-pyrene — M.C. Jaurand, L. Magne, et al. (1981)
• Effects of chrysotile on a lysosomal enzyme preparation and on the hydrolytic enzyme activity of cultured alveolar macrophages — R. Desai, R.J. Richards (1983)
• Pleural Effusion of Patients with Malignant Mesothelioma Induces Macrophage-Mediated T Cell Suppression — L.A. Lievense, R. Cornelissen, et al. (2016)
• Macrophage stimulation and the inflammatory response to asbestos — J.A. Hamilton (1980)

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