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The receptor for urokinase-type plasminogen activator is deficient on
peripheral blood leukocytes in patients with paroxysmal nocturnal
hemoglobinuria
M Ploug, T Plesner, E Ronne, V Ellis, G Hoyer-Hansen, NE Hansen and K Dano
Finsen Laboratory, Copenhagen, Denmark.
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.
Volume 79,
Issue 6,
pp. 1447-1455,
03/15/1992
Copyright © 1992 by The American Society of Hematology
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