Macrophage production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
Open Access
- 1 September 1989
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 170 (3), 727-737
- https://doi.org/10.1084/jem.170.3.727
Abstract
A rat model of bleomycin-induced pulmonary inflammation and fibrosis was used to examine the relationship between collagen synthesis and transforming growth factor beta (TGF-beta) production, and cellular distribution. Total lung TGF-beta was elevated within 2 h of intratracheal bleomycin administration and peaked 7 d later at levels 30-fold higher than controls. This was followed by a gradual decline with lower but persistent levels of production in the late phase of the response between 21 and 28 d later. The peak TGF-beta levels preceded the maximum collagen and noncollagen protein synthesis measured by [3H]proline incorporation into lung fibroblast explants of bleomycin-treated rats. The pattern of immunohistochemical staining localized TGF-beta initially in the cytoplasm of bronchiolar epithelium cells and subepithelial extracellular matrix. The peak of lung TGF-beta levels at 7 d coincided with intense TGF-beta staining of macrophages dispersed in the alveolar interstitium and in organized clusters. Later in the course of the response. TGF-beta was primarily associated with extracellular matrix in regions of increased cellularity and tissue repair, and coincided with the maximum fibroblast collagen synthesis. This temporal and spatial relationship between collagen production and TGF-beta production by macrophages suggests an important if not primary role for TGF-beta in the pathogenesis of the pulmonary fibrosis.Keywords
This publication has 26 references indexed in Scilit:
- Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice.The Journal of cell biology, 1989
- Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.Online Journal of Public Health Informatics, 1986
- Profiles of steady state levels of messenger RNAs coding for type I procollagen, elastin, and fibronectin in hamster lungs undergoing bleomycin-induced interstitial pulmonary fibrosis.JCI Insight, 1985
- Bleomycin selectively elevates mRNA levels for procollagen and fibronectin following acute lung injuryBiochemical and Biophysical Research Communications, 1985
- Morphometric estimates of infiltrative cellular changes during the development of bleomycin-induced pulmonary fibrosis in hamsters.1983
- Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization.Journal of Biological Chemistry, 1983
- Interstitial lung disease: Current concepts of pathogenesis, staging and therapyThe American Journal of Medicine, 1981
- Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.1979
- Bleomycin-induced pulmonary fibrosis in the rat: inhibition by indomethacin.1979
- Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Lung volumes, volume-pressure relations, carbon monoxide uptake, and arterial blood gas studied.Published by Elsevier BV ,1978