Defective regulation of complement by the sickle erythrocyte: evidence for
a defect in control of membrane attack complex formation
ST Test and VS Woolworth
Children's Hospital Oakland Research Institute, CA 94609.
A prominent clinical manifestation of sickle cell disease (SCD) is
hemolytic anemia. Although complement activation can lead to intravascular
hemolysis, its role in the hemolysis of SCD is not known. Because normal
red blood cells induced to vesiculate by treatment with calcium and
ionophore become sensitive to damage by activated complement and because
sickle cells release microvesicles as they circulate, we postulated that
sickle cells might also be unusually sensitive to complement-dependent
hemolysis. Complement activation is tightly regulated on the membrane of
the normal erythrocyte; therefore, defective complement regulation by the
sickle cell would be necessary for complement-dependent hemolysis to occur.
These studies show a defect in the regulation of membrane attack complex
(C5b-9) formation in sickle erythrocytes, particularly in the most dense
cells. The defect is characterized by increased binding of C5b-7 and of C9
to denser sickle cells and results in increased susceptibility of sickle
cells to C5b-9-mediated (reactive) lysis initiated by either C5b6 or
activated cobra venom factor. Among the densest sickle cells, irreversibly
sickled cells are especially sensitive to reactive lysis. The similarity of
this defect to that previously described in a patient with paroxysmal
nocturnal hemoglobinuria suggests that complement- mediated hemolysis could
play a role in the anemia of SCD.
Volume 83,
Issue 3,
pp. 842-852,
02/01/1994
Copyright © 1994 by The American Society of Hematology
