The mast cell as site of tissue-type plasminogen activator expression and fibrinolysis

Recent data suggest that mast cells (MC) and their products (heparin, prote ases) are involved in the regulation of coagulation and fibrino(geno)lysis. The key enzyme of fibrinolysis, plasmin, derives from its inactive progeni tor, plasminogen, through catalytic action of plasminogen activators (PAs), In most cell systems, however, PAs are neutralized by plasminogen activato r inhibitors (PAIs), We report that human tissue MC as well as the MC line HMC-1 constitutively produce, express, and release tissue-type plasminogen activator (tPA) without producing inhibitory PAIs. As assessed by Northern blotting, highly enriched lung MG (>98% pure) as web as HMC-1 expressed tPA mRNA, but did not express mRNA for PAI-1, PAI-2, or PAI-3, The tPA protein was detectable in RIG-conditioned medium by Western blotting and immunoass ay, and the MC agonist stem cell factor (c-Kit ligand) was found to promote the release of tPA from MG, In addition, RIG-conditioned medium induced fi brin-independent plasmin generation as well as clot lysis in vitro. These o bservations raise the possibility that MC play an important role in endogen ous fibrinolysis.