Environmental Health Perspectives 105, Supplement 5, September 1997

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Immunohistochemical Localization of Transforming Growth Factor Beta Isoforms in Asbestos-Related Diseases

Jaishree Jagirdar, 1 Theodore C. Lee, 2 Joan Reibman, 2 Leslie I. Gold, 1 Christopher Aston, 2 Raymond Bégin, 3 and William N. Rom 2

1 Department of Pathology; 2 Department of Medicine, New York University Medical Center, New York, New York
3 Unité de Recherche Pulmonaire, Université de Sherbrooke, Québec, Canada

Abstract
Transforming growth factor beta (TGF-ß), a multifunctional cytokine and growth factor, plays a key role in scarring and fibrotic processes because of its ability to induce extracellular matrix proteins and modulate the growth and immune function of many cell types. These effects are important in inflammatory disorders with fibrosis and cancer. The asbestos-related diseases are characterized by fibrosis in the lower respiratory tract and pleura and increased occurrence of lung cancer and mesothelioma. We performed immunohistochemistry with isoform-specific antibodies to the three TGF-ß isoforms on 16 autopsy lungs from Quebec, Canada, asbestos miners and millers. There was increased immunolocalization of all three TGF-ß isoforms in the fibrotic lesions of asbestosis and pleural fibrosis. The hyperplastic type II pneumocytes contained all three isoforms. By contrast, there was differential spatial immunostaining for the TGF-ß isoforms in malignant mesothelioma, with TGF-ß1 in the stroma but TGF-ß2 in the tumor cells. These data are consistent with an important role for TGF-ß in accumulation of extracellular matrix and cell proliferation in asbestos-related diseases. -- Environ Health Perspect 105(Suppl 5):1197-1203 (1997)

Key words : transforming growth factor-ß, asbestosis, pleural fibrosis, mesothelioma

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 14 July 1997.

The authors thank N. Little for editorial assistance. This work was supported by National Institutes of Health grant MO1 RR00096, Con Edison, and National Institute for Occupational Safety and Health grant U60/CC206153.

Address correspondence to Dr. W.N. Rom, Division of Pulmonary and Critical Care Medicine, New York University Medical Center, 550 First Avenue, New York, NY 10016. Telephone: (212) 263-6479. Fax: (212) 263-8442. E-mail: romw01@mcgc.16.med.nyu.edu

Abrreviations used: AM, alveolar macrophage(s); BSA, bovine serum albumin; CDK, cyclin-dependent kinase; IGF, insulinlike growth factor; IPF, idiopathic pulmonary fibrosis; Rb, retinoblastoma; TBS, tris-buffered saline; TGF-ß, transforming growth factor beta.

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Last Update: November 1, 1997