Significance of thrombin in bleomycin-induced pulmonary fibrosis.
To clarify the role of thrombin in fibroblast growth and the development of pulmonary fibrosis in bleomycin-induced interstitial lung disease, we examined the relationship of thrombin activity to fibroblast growth-stimulating activity (FGA) in bronchoalveolar lavage fluid (BALF) from bleomycin-treated rats. Male Wistar rats were given a single intratracheal injection of bleomycin, bronchoalveolar lavage was performed 2, 6 and 15 days later, and the BALF was assayed for thrombin activity and FGA. Higher FGA than the control value was detected in the BALF from rats on Day 6 after bleomycin administration. In bleomycin-treated rats, thrombin activity in the BALF was significantly elevated on Day 2, and maximal on Day 6. The FGA of the BALF from bleomycin-treated rats on Day 6 was significantly decreased by its treatment with various thrombin inhibitors, such as alpha 1-antitrypsin, antithrombin III, hirudin and MD-805. On ammonium sulfate fractionation most of the thrombin activity was recovered in the fraction of 35-50% saturation in which most of the FGA was detected. These results suggest that the FGA of the BALF from bleomycin-treated rats was at least partly due to thrombin, and that thrombin is responsible, at least in part, for fibroblast growth and pulmonary fibrosis in bleomycin-induced interstitial lung disease.
3rd Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
K
K
Tani
S
S
Yasuoka
T
T
Ogura
D000818:Animals; D001761:Bleomycin / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D001761:Bleomycin; D005346:Fibroblast Growth Factors; D013917:Thrombin