Procoagulant activity of alveolar macrophages in bleomycin-induced lung fibrosis in rats

Abstract

Interstitial and intraalveolar fibrin deposition is a prominent feature in adult respiratory distress syndrome and is also observed in the inflammatory phase of interstitial lung disease (ILD). It is suggested that the coagulation abnormality in these disorders may be implicated in the pathogenesis of subsequent fibrosis of the lung. In this study, we examined the procoagulant activity (PCA) of alveolar macrophages during the development of bleomycin-induced lung fibrosis in rats. The PCA of alveolar macrophages was significantly increased at 2, 7 and 14 days after the intratracheal administration of bleomycin compared with that of control rats. The greatest PCA was observed at 7 days after the bleomycin injection, the inflammatory phase in the development of lung fibrosis. Increased PCA returned to the normal value at 21 days, while the fibrotic process advanced and the collagen content increased in the lung. Alveolar macrophages at 7 days after the administration of bleomycin or saline were separated into five density fractions on discontinuous Percoll gradients. The increase in the percentage of low-density macrophages was observed in bleomycin-injected rats. The greatest PCA was demonstrated in the lowest-density fraction (specific gravity less than 1.030), while reduced activities were observed in the higher-density fractions, in each group. The increased PCA of alveolar macrophages during lung injury was due in part to the increase of low-density subpopulation, which had greater PCA, although the fibrin deposition in the development of lung fibrosis remained to be defined, the increase of coagulation pathways may contribute to the progression of interstitial fibrotic lung diseases.