INCREASED SECRETION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR BY HUMAN LUNG MICROVASCULAR ENDOTHELIAL-CELLS

Human lung microvascular endothelial cells (HLMECs) secreted 1.5-15 ti mes more urokinase-type plasminogen activator (uPA) antigen than human hepatic microvascular endothelial cells, human umbilical vein endothe lial cells (HUVECs), angioma endothelial cells, and lung fibroblasts. All of these cells also secreted a 100-fold greater amount of plasmino gen activator inhibitor-1 than of uPA antigen, and uPA activities were not detected in the culture medium. The expression of uPA mRNA in HLM ECs was higher (100-fold) compared with HUVECs, angioma endothelial ce lls, and lung fibroblasts. HLMECs secreted uPA antigen on both the lum inal and basal sides of the cells. On the other hand, HLMECs secreted a 10- to 15-fold lower amount of tissue-type plasminogen activator tha n HUVECs, mostly on the luminal side. After stimulation with interleuk in (IL)-1 beta, HLMECs secreted a six- to ninefold amount of uPA antig en. In contrast, no stimulatory effect was observed in HUVECs even und er high IL-1 beta concentrations. The secretion of uPA and plasminogen activator inhibitor-1 from HLMECs was also enhanced by tumor necrosis factor-alpha and IL-2. These results suggest that HLMECs may contribu te not only to the patency of lung vessels but also to the maintenance of alveolar functions through the production and secretion of uPA, es pecially in the presence of inflammatory cytokines.