The receptor for urokinase-type plasminogen activator is deficient on peripheral blood leukocytes in patients with paroxysmal nocturnal hemoglobinuria.

摘要: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect in bone marrow-derived cells and clinically associated with intravascular hemolysis, hemoglobinuria, increased frequency of venous thrombosis. The common denominator PNH-affected blood appears to be a the membrane attachment proteins normally anchored by glycosyl-phosphatidylinositol (GPI). We report here that cellular receptor for urokinase-type plasminogen activator (u-PAR) deficient on affected peripheral monocytes granulocytes from four individuals PNH as evidenced chemical cross-linking analysis well immunofluorescence flow cytometry using monoclonal anti-u-PAR antibody. In contrast, normal we find significant amounts u-PAR, which attached plasma GPI-anchor defined its sensitivity towards specific phospholipase treatment. By two-color it was shown deficiency u-PAR expression paralleled another GPI-anchored protein. As involved initiation pericellular proteolysis, reduced leukocytes led overall reduction capacity activation cell-surface-bound urokinase. Whereas abnormal susceptibility erythrocytes lysis autologous complement has been related low three regulatory cell surface, now propose lack surface may causally high incidence thrombosis observed patients.