THE RECEPTOR FOR UROKINASE PLASMINOGEN-ACTIVATOR IS PRESENT IN PLASMAFROM HEALTHY DONORS AND ELEVATED IN PATIENTS WITH PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA

The urokinase plasminogen activator (uPA) is a proteolytic enzyme whic h converts the proenzyme plasminogen to the active serine protease pla smin. A cell surface receptor for uPA (uPAR) is attached to the cell m embrane by a glycosyl-phosphatidylinositol anchor. Binding of uPA to u PAR leads to an enhanced plasmin formation and thereby an amplificatio n of pericellular proteolysis. We have shown previously that uPAR is e xpressed on normal blood monocytes and granulocytes, but is deficient on affected blood monocytes and granulocytes in patients with paroxysm al nocturnal haemoglobinuria (PNH), and that uPAR is present in plasma from these patients. In this study a newly established sensitive enzy me-linked immunosorbent assay (ELISA) has been applied for quantitatio n of uPAR in plasma. Unexpectedly, we found that uPAR is not only pres ent in PNH plasma but also in plasma from healthy individuals. In 39 h ealthy individuals the mean plasma-uPAR value +/- SD was 31 +/- 15 pM, median 28 (range 11-108), and the corresponding value for six PNH pat ients was 116 +/- 67 pM, median 90 (range 61-228). The elevated uPAR-l evel in PNH patients was highly significant (Mann-Whitney test; P < 0. 0001), and may possibly contribute to the propensity for thrombosis in PNH by inhibition of the fibrinolytic system. Binding of pro-uPA by u PAR in plasma may interfere with the appropriate binding of pro-uPA to cell-bound uPAR and therefore inhibit cell-associated plasmin generat ion and fibrinolysis. It is likely that the uPAR in normal plasma refl ects the overall level of activity of the uPAR-mediated cell surface p roteolysis. The present ELISA may be used for studies of uPAR levels i n plasma from patients with conditions in which this activity might be increased, such as cancer and inflammatory disorders. Future studies will determine if uPAR in plasma is a parameter of clinical importance in these diseases.