Immunohistochemical localization of transforming growth factor-β and insulin-like growth factor-I in asbestosis in the sheep model

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Asbestosis is characterized by increased collagen deposition along the walls of terminal respiratory bronchioles that extends into the alveolar ducts and septae. Alveolar macrophages are activated and release growth factors that stimulate mesenchymal cell proliferation and enhanced formation of extracellular matrix. Both insulin-like growth factor-I (IGF-I), and transforming growth factor β (TGF-β) regulate cellular growth and promote matrix accumulation and are hypothesized to play important roles in asbestosis. We performed immunohistochemistry using polyclonal antibodies to specific synthetic peptides of the three mammalian isoforms of TGF-β (TGF-β1, -β2, -β3) and to IGF-I on lungs of sheep treated intratracheally with chrysotile asbestos. All three TGF-β isoforms were found in bronchial and bronchiolar epithelium, macrophages, and bronchial and vascular smooth muscle in control lungs. The distribution of TGF-β was increased in these lung constituents as fibrotic lesions developed. Fibrotic lesions additionally demonstrated intense immunostaining of all three TGF-β isoforms that localized to the extracellular matrix zones with little staining of interstitial cells. In the control sheep lungs, IGF-I staining was detected in bronchial and bronchiolar epithelium, bronchial glands, bronchial and vascular smooth muscle, endothelium, and macrophages. IGF-I immunostaining was detected in macrophages in peri-bronchial fibrosis and in fibroblasts along the periphery of and within lesions, but not in the extracellular matrix. Metaplastic proliferating epithelium and macrophages were strongly immunoreactive for IGF-I in advanced lesions. Our data demonstrate different immunostaining patterns for IGF-I and TGF-β in asbestosis, with IGF-I in the cellular periphery and TGF-β in the extracellular matrix consistent with a complementary role in stimulating interstitial fibroblast proliferation and new collagen deposition in areas of active fibrosis.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalInternational Archives of Occupational and Environmental Health
Issue number3
StatePublished - Mar 1997


  • Insulin-like growth factor I
  • Pulmonary fibrosis
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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