Environmental Health Perspectives 105, Supplement 5, September 1997

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Involvement of Protein Kinase C, Phospholipase C, and Protein Tyrosine Kinase Pathways in Oxygen Radical Generation by Asbestos-stimulated Alveolar Macrophage

Young Lim, 1 Sun-Hyung Kim, 2 Kyoung-Ah Kim, 1 Min-Wha Oh, 3 and Kweon-Haeng Lee 2

1 Department of Industrial Medicine, St. Mary's Hospital, Catholic University Medical College, Seoul, Korea
2 Department of Pharmacology, Catholic University Medical College, Seoul, Korea
3 Department of Preventive Medicine, Inha General Hospital, Songnam, Korea

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. -- Environ Health Perspect 105(Suppl 5):1325-1327 (1997)

Key words : macrophage, asbestos, protein kinase C, phospholipase C, protein tyrosine kinase

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 6 June 1997.

This study was supported by grant HMP-96-M-1-1008 of the 1996 Good Health Research and Development Project Ministry of Health Welfare, Republic of Korea.

Address correspondence to Dr. Y. Lim, Department of Industrial Medicine, St. Mary's Hospital, Catholic University Medical College, 62 Yoido-dong, Youngdungpo-gu, Seoul 150-010, Korea. Telephone: 82 2 789 1401. Fax: 82 2 782 6017. E-mail: nglim@cmc.cuk.ac.kr

Abbreviations used: AM, alveolar macrophage(s); DAG, diacylglycerol; DMSO, dimethyl sulfoxide; HBSS, Hanks balanced salt solution; IP 3 , inositol triphosphate; LPS, lipopolysaccharide; PI, phosphoinositide; PIP 2 , phosphatidyl inositol biphosphate; PKC, protein kinase C; PLC, phospholipase C; PTK, protein tyrosine kinase.

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Last Update: November 28, 1997