Thrombin stimulates platelet-derived growth factor release by alveolar macrophages in rats : significance in bleomycin-induced pulmonary fibrosis

Thrombin is a multifunctional enzyme generated at sites of vascular injury, and is known to be increased in the lungs in some types of fibrotic lung disease. In this study, to determine whether thrombin is associated with fibroblast growth and pulmonary fibrosis in these disorders, we examined whether a growth factor for fibroblasts (platelet-derived growth factor, PDGF) was released by thrombin-stimulated alveolar macrophages (AM). The culture supernatants of rat AM stimulated with 1 or 10 U/ml of thrombin showed a significant increase in fibroblast growth-stimulating activity (FGA). Pretreatment of the AM supernatant with anti-PDGF-AA antibody significantly decreased the FGA, but pretreatment with anti-PDGF-BB antibody did not. The supernatants of AM stimulated with thrombin also increased the growth of fibroblasts from the lungs of rats with bleomycin-induced lung injury. These results indicate that thrombin stimulates AM to release PDGF-AA, which is responsible, at least in part, for fibroblast growth and the development of pulmonary fibrosis in some types of fibrotic lung disease.