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.