The control of complement activation by the blood cells in paroxysmal nocturnal hemoglobinuria.
نویسنده
چکیده
By Wendell F. Rosse S INCE THE CLASSIC studies of Ham and Dingle,’ it has been known that the red blood cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) are unusually susceptible to the hemolytic action of complement. There are two major types of abnormal cells in this syndrome: the PNH II red blood cells are moderately sensitive to the lytic action of complement (three to six times more sensitive than normal red blood cells),2 and the PNH ill red blood cells are markedly sensitive to complement ( 1 5 to 25 times more sensitive than normal cells).3’4 The platelets5’6 and granubocytes5’7 are also more sensitive although the degree of abnormality is less well defined than for red cells. The reason for this unusual susceptibility has remained elusive. The increased lysis could not be attributed to increased binding of antibody or to increased activation of any of the first three components.8 It has been demonstrated that when complement is activated on the surface of both varieties of abnormal red cells,”9 platelets,6 and granubocytes,7 an abnormally large amount of C3 is deposited on the membrane. For red cells, this component is deposited primanly on the glycoproteins of the membrane,’#{176} and although these may be abnormal, they do not provide an acceptor surface that attracts activated C3b abnormally. The activation of complement on the surface of red blood cells is regulated by a series of reactions” that tend to inactivate the complexes formed by that activation. One such inactivation reaction is due to the presence of a glycoprotein, decay-accelerating factor (DAF), on the surface of the red cell’2”3 that either prevents the formation of the C3 convertase complexes (C4b2a and C3bBb) or facilitates their disruption and thus their inactivation. Recently, it has been shown that DAF is absent on both PNH II and PNH III red cells as well as platelets and granulocytes in PNH.’ ’7 This defect probably accounts for the increased binding of C3 since inhibition of the activity of DAF by antibody results in a marked increase in binding of C3 as is seen in PNH II and PNH III cells.’8 The deficiency of DAF appears to be acquired during maturation of the red cells since it apparently is not deficient on the surface of early red cell precur-
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ورودعنوان ژورنال:
- Blood
دوره 67 2 شماره
صفحات -
تاریخ انتشار 1986