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

Our plain-English summary of Immunohistochemical localization of transforming growth factor-beta and insulin-like growth factor-I in asbestosis in the sheep model, by T.C. Lee, L.I. Gold, J. Reibman, et al (International Archives of Occupational and Environmental Health, 1997).

The study

• Authors: T.C. Lee, L.I. Gold, J. Reibman, C. Aston, R. Bégin, W.N. Rom, J. Jagirdar
• Journal: International Archives of Occupational and Environmental Health
• Published: 1997;69(3):157-64
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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 beta (TGF-beta) 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-beta (TGF-beta 1, -beta 2, -beta 3) and to IGF-I on lungs of sheep treated intratracheally with chrysotile asbestos. All three TGF-beta isoforms were found in bronchial and bronchiolar epithelium, macrophages, and bronchial and vascular smooth muscle in control lungs. The distribution of TGF-beta was increased in these lung constituents as fibrotic lesions developed. Fibrotic lesions additionally demonstrated intense immunostaining of all three TGF-beta 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 peribronchial 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-beta in asbestosis, with IGF-I in the cellular periphery and TGF-beta in the extracellular matrix consistent with a complementary role in stimulating interstitial fibroblast proliferation and new collagen deposition in areas of active fibrosis.

In plain English

This was an animal experiment in sheep. Fifteen sheep had 100 mg of UICC Canadian chrysotile asbestos placed into the windpipe every 2 weeks, and 10 control sheep received salt solution only. After 1 year the exposed sheep were split into low, intermediate and high-dose groups of five. They were killed at the end of the second year. The authors used antibody staining on lung tissue to see where two growth factors were found: TGF-beta (three forms) and IGF-I. Low-dose lungs showed occasional mild inflammation. High-dose lungs showed interstitial fibrosis and focal honeycombing. Unexposed lungs had TGF-beta in lesser amounts. In scarred areas, TGF-beta was found mainly in the extracellular matrix, the material between cells. IGF-I was found in fibroblasts around and within lesions but not in the matrix. The authors concluded that the two factors are complementary and may work together. They said further tests are needed to prove that more TGF-beta is actually produced.

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: Animal experiment (sheep model of asbestosis) using immunohistochemistry, meaning antibody staining of lung tissue
• Who was studied: 25 sheep: 10 controls given phosphate-buffered saline and 15 given chrysotile asbestos. Location and dates of the experiment are not stated.
• Exposure: UICC Canadian chrysotile asbestos, 100 mg in 100 ml saline every 2 weeks by intratracheal instillation for 1 year. Then three groups of five sheep each continued as follows until the end of the second year: low (no further asbestos), intermediate (10 mg every 10 days) and high (100 mg every 10 days).
• Main results:
  • Low-dose group: occasional mild increase in inflammatory cells in alveoli and around airways.
  • Intermediate-dose group: inflammation, alveolitis with many macrophages, and focal honeycombing.
  • High-dose group: increased cellularity, interstitial fibrosis and focal honeycombing. Control sheep had normal lung histology.
  • Asbestos fibers were visible in only 2 of the 5 low-dose sheep. In the high-dose group, fibers were present in practically all microscope fields.
  • TGF-beta was present in lungs of unexposed control sheep, in lesser amounts.
  • In asbestos-exposed sheep, all three TGF-beta forms were found mainly in the extracellular matrix of scarred lesions around the small airways, with occasional fibroblasts also stained.
  • In advanced disease, TGF-beta3 staining was seen in hyperplastic type II pneumocytes (a type of lung lining cell).
  • In unexposed control sheep, IGF-I was found in airway lining cells and glands, among other sites.
  • In scarred lesions, IGF-I was found in fibroblasts at the edges of lesions and in fewer fibroblasts within them.
  • Unlike TGF-beta, IGF-I was not found in the extracellular matrix.
  • In more advanced lesions, metaplastic proliferating epithelium, fibroblasts and macrophages stained heavily for IGF-I. These data were not shown in the article.
• The authors' conclusion: The authors concluded that IGF-I and TGF-beta in these lesions are complementary and may act together (synergistically) in the development of fibrosis.
• Limitations the authors state:
  • The authors stated that further studies using in situ hybridization or quantitative PCR are needed to prove increased production of TGF-beta, beyond showing where it is located.
  • The authors described their idea that IGF release may help release active TGF-beta as speculative.

Topics

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

Medical terms in this study, explained in our Lexicon: Transforming Growth Factor-beta (TGF-β), Collagen, Deposition, Alveolar Macrophage, Immunohistochemistry, Chrysotile, Epithelium, Macrophage.

Related studies

• Immunohistochemical localization of transforming growth factor beta isoforms in asbestos-related diseases — J. Jagirdar, T.C. Lee, et al. (1997)
• Solitary fibrous tumor of the pleura. An immunohistochemical, electron microscopic and tissue culture study of a tumor producing insulin-like growth factor I in a patient with hypoglycemia — E.H. Strøm, F. Skjørten, et al. (1991)
• Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats — T.D. Perdue, A.R. Brody (1994)
• Activated alveolar macrophages express the insulin-like growth factor-I receptor — W.N. Rom, P. Pääkkö (1991)
• Transforming growth factor-beta 1 (TGF-beta 1)- and beta 2-like activities in malignant pleural effusions caused by malignant mesothelioma or primary lung cancer — J. Maeda, N. Ueki, et al. (1994)
• Transforming growth factor-beta(1) overexpression in tumor necrosis factor-alpha receptor knockout mice induces fibroproliferative lung disease — J.Y. Liu, P.J. Sime, et al. (2001)

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