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

Content Provider	Scilit
Author	Ploug, M. Plesner, T. Ronne, E. Ellis, V. Hoyer-Hansen, G. Hansen, Ne Dano, K.
Copyright Year	1992
Description	Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect in bone marrow-derived cells and is clinically associated with intravascular hemolysis, hemoglobinuria, and an increased frequency of venous thrombosis. The common denominator of PNH-affected blood cells appears to be a defect in the membrane attachment of proteins normally anchored by glycosyl-phosphatidylinositol (GPI). We report here that the cellular receptor for urokinase-type plasminogen activator (u-PAR) is deficient on affected peripheral blood monocytes and granulocytes from four individuals with PNH as evidenced by chemical cross-linking analysis as well as by immunofluorescence flow cytometry using a monoclonal anti-u-PAR antibody. In contrast, on normal blood monocytes and granulocytes we find significant amounts of u-PAR, which is attached to the plasma membrane by a GPI-anchor as defined by its sensitivity towards a specific phospholipase treatment. By two-color flow cytometry it was shown that deficiency of u-PAR expression paralleled that of another GPI-anchored protein. As u-PAR is involved in the initiation of pericellular proteolysis, the reduced expression of u-PAR on PNH-affected leukocytes led to an overall reduction in the capacity for plasminogen activation by cell-surface-bound urokinase. Whereas the abnormal susceptibility of PNH-affected erythrocytes to lysis by autologous complement has been related to the low expression of three GPI-anchored complement regulatory proteins on the cell surface, we now propose that lack of u-PAR expression on the surface of peripheral blood leukocytes may be causally related to the high incidence of venous thrombosis observed in PNH patients.
Related Links	https://ashpublications.org/blood/article-pdf/79/6/1447/617822/1447.pdf
Ending Page	1455
Page Count	9
Starting Page	1447
DOI	10.1182/blood.v79.6.1447.1447
Journal	Blood
Issue Number	6
Volume Number	79
Language	English
Publisher	American Society of Hematology
Publisher Date	1992-03-15
Access Restriction	Open
Subject Keyword	Hematology Proteins Bone Marrow Urokinase Pnh Plasminogen Activator Hemoglobinuria Peripheral Deficient Venous Thrombosis Journal: Blood (Vol- 89, Issue- 6)
Content Type	Text
Resource Type	Article