Enhanced complement-mediated lysis of type III paroxysmal nocturnal hemoglobinuria erythrocytes involves increased C9 binding and polymerization.
The interaction of terminal complement proteins (C5-C9) with normal erythrocytes and type III paroxysmal nocturnal hemoglobinuria erythrocytes (PNH-E) has been compared in terms of binding of the C5-9 complex, C9 polymerization, and C9 insertion into membranes. Complement components C5, C7, and C8 bind equally well to both types of erythrocytes, whereas the binding of C9 to PNH-E is 5-6 times greater than that to normal erythrocytes. The kinetics of C9 binding was compared with the kinetics of lysis for both types of cells under conditions leading to 100% lysis. There was a noticeable lag time between C9 binding and lysis of normal erythrocytes, but the lysis of PNH-E proceeded without a lag and the kinetics of lysis more closely paralleled C9 binding. The efficiency of C9 insertion was similar for both types of cells, but C9 polymerization was significantly enhanced on PNH-E. These data indicate that the enhanced susceptibility of type III PNH-E toward lysis by C5-9 can be correlated with abnormally high C9 binding and increased formation of poly(C9).
D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D003186:Complement C9 / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004912:Erythrocytes / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D012016:Reference Values
D002352:Carrier Proteins; D003186:Complement C9; D046911:Macromolecular Substances; D003165:Complement System Proteins