Reduced Fibrinolytic Activity in Bronchoalveolar Lavage Fluids is not Related to Alveolar Macrophages in the Fibrosis of Interstitial Pneumonia : An Analysis of Bronchoalveolar Lavage Fluids

Reduced fibrinolytic activity in the alveolar space of patients with interstitial pneumonia (IP) is considered the key factor in the development of pulmonary fibrosis. However, the origin of this fibrinolytic activity and its relationship to the fibrosis in IP is still unclear. Levels of the urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen were measured in bronchoalveolar lavage fluids (BALF) obtained from patients with IP, and the data were compared between the two groups (fibrosing group and non-fibrosing group) based mainly on honeycomb formation revealed by pulmonary high-resolution computed tomography (HRCT) and partially on lung histology. In addition, the cell surface plasmin generation of various alveolar macrophages (AM) and its correlation with the u-PA/PAI-1 levels in each of the two groups were studied. The u-PA level was significantly lower in BALF from IP patients than from sarcoidosis patients with no interstitial shadows on HRCT used as the contols. Although u-PA and PAI-1 levels did not differ between the fibrosing and the non-fibrosing group, the macrophage count and the percentage of macrophages in BALF were significantly greater in the fibrosing group. The major regulatory cytokines, interleukin 1-β and transforming growth factor-β, however, did not affect cell surface plasmin generation by AM, indicating that the AM-related fibrinolytic activity was constant. These results indicate that the decreased fibrinolytic activity in BALF is not related to AM although it is associated with the fibrosis of IP. We speculate that other cells such as alveolar epithelial cells contribute to the fibrosis although further clinical studies will be required.