Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage

Our plain-English summary of Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage, by Y. Lim, S.H. Kim, K.A. Kim, et al (Environmental Health Perspectives, 1997).

The study

• Authors: Y. Lim, S.H. Kim, K.A. Kim, M.W. Oh, K.H. Lee
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1325-7
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Although asbestos stimulates oxygen radical generation in alveolar macrophages, the exact mechanism is still not clear. The purpose of this study was to compare the ability of three asbestos fibers (amosite, chrysotile, and crocidolite) to generate oxygen radicals in macrophages and examine the mechanism of this action. All asbestos fibers were able to induce chemiluminescence but chrysotile induced maximal chemiluminescence at higher concentrations than amosite and crocidolite. Protein kinase C (PKC) inhibitors (sphingosine and staurosporine) suppressed the ability of asbestos to induce oxygen radical generation. Phospholipase C (PLC) inhibitors (U73122 and neomycin) and protein tyrosine kinase (PTK) inhibitors (erbstatin and genistein) decreased oxygen radical generation of asbestos-stimulated alveolar macrophages. Oxygen radical generation was not suppressed by an adenylate cyclase activator (forskolin), a protein kinase A inhibitor (H-8), and a protein serine-threonine phosphatase inhibitor (okadaic acid). PLC and PTK inhibitors suppressed the increment of phosphoinositide turnover by amosite. These results suggest that asbestos fibers induce the generation of oxygen radicals through PTK, PLC, and PKC pathways in a dose-response pattern.

In plain English

This was a laboratory experiment on alveolar macrophages, immune cells washed out of the lungs of male Sprague-Dawley rats. The cells were primed beforehand with bacterial lipopolysaccharide. Seven rats were used for the oxygen radical tests and two for an enzyme activity test. The cells were exposed to reference samples of amosite, crocidolite and chrysotile, and the release of oxygen radicals was measured by light emission (chemiluminescence). All three fibers produced this response. Amosite gave its highest level at a lower dose, and the authors reported that the amphiboles were stronger at lower doses than chrysotile, a serpentine fiber. Drugs that block protein kinase C, phospholipase C or protein tyrosine kinase reduced or abolished the response. A calcium channel blocker cut it to about 40% of control values. Three other drugs did not change it. The authors concluded that asbestos stimulated oxygen radical generation in these cells through protein tyrosine kinase, phospholipase C and protein kinase C pathways, and that intracellular calcium might play a role.

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 (cell) experiment using alveolar macrophages taken from rats
• Who was studied: Alveolar macrophages from male Sprague-Dawley rats (250-300 g), primed with lipopolysaccharide 20 hours before collection. Seven rats were used for chemiluminescence and two for phospholipase C activity. The research was carried out at Catholic University Medical College, Seoul, Korea. Dates are not given.
• Exposure: Crocidolite, amosite and chrysotile (UICC reference standard samples), added to the cultured cells. Table 1 used amosite and crocidolite at 5 mg/ml and chrysotile at 10 mg/ml. Amosite at 20 mg/ml was used for the phospholipase C activity test.
• Main results:
  • All three fibers induced chemiluminescence. Amosite showed the highest level at a lower dose, and the authors reported that the amphiboles were stronger at lower doses than serpentine fibers (chrysotile).
  • For all three fibers, the calcium channel blocker verapamil inhibited asbestos-induced chemiluminescence to approximately 40% of control values (Table 1).
  • The protein kinase C inhibitors sphingosine and staurosporine suppressed asbestos-induced chemiluminescence for all three fibers. Sphingosine suppressed it completely, and staurosporine had nearly identical effects.
  • The phospholipase C inhibitors reduced but did not completely suppress chemiluminescence. U73122 reduced it to approximately 40% of control values, and neomycin reduced it to between 20 and 40% of control values.
  • The protein tyrosine kinase inhibitors genistein and erbstatin suppressed asbestos-induced chemiluminescence. The authors suggested that a protein tyrosine kinase pathway is involved.
  • Okadaic acid (a serine-threonine phosphatase inhibitor), H-8 (a protein kinase A inhibitor) and forskolin (an adenylate cyclase activator) did not change asbestos-induced chemiluminescence.
  • In amosite-stimulated cells, phosphoinositide turnover was 241 counts per minute in controls. It was 101 with neomycin and 99 with U73122, which the authors described as complete suppression. It was 197 with genistein and 121 with erbstatin. All four reductions were reported as significantly different from control.
• The authors' conclusion: The authors concluded that different asbestos fibers induced oxygen radical generation with different dose-response patterns, that asbestos stimulated oxygen radical generation in alveolar macrophages through protein tyrosine kinase, phospholipase C and protein kinase C pathways, and that intracellular calcium might play an important role.

Topics

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

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Amosite, Chrysotile, Crocidolite, Macrophage, Dose-response relationship.

Related studies

• Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-alpha response from alveolar macrophages — P.P. Simeonova, M.I. Luster (1995)
• Activation of alveolar macrophages and peripheral red blood cells in rats exposed to fibers/particles — F. Afaq, P. Abidi, et al. (1998)
• Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres — L.C. Mongan, T. Jones, et al. (2000)
• Nitric oxide (NO) synthase activity in the lung and NO synthesis in alveolar macrophages of rats increased on exposure to asbestos — H. Iguchi, S. Kojo, et al. (1996)
• Cellular mechanisms of reactive oxygen metabolite generation from human polymorphonuclear leukocytes induced by crocidolite asbestos — T. Ishizaki, E. Yano, et al. (1997)
• A protein kinase Cdelta-dependent protein kinase D pathway modulates ERK1/2 and JNK1/2 phosphorylation and Bim-associated apoptosis by asbestos — S.A. Buder-Hoffmann, A. Shukla, et al. (2009)

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