Paroxysmal nocturnal hemoglobinuria type III. Lack of an erythrocyte membrane protein restricting the lysis by C5b-9.
The complement-mediated lysis is inefficient when complement and target cells are homologous with regard to the species. In erythrocytes from patients suffering from paroxysmal nocturnal hemoglobinuria (PNH), the species restriction is lost: PNH-erythrocytes (PNH-E) are susceptible to lysis by human complement. In human erythrocytes (huE) the species restriction is ascribed to an integral membrane protein, designated C8-binding protein (C8bp). In the present study, we tested membranes of PNH-E type III for the presence of C8bp. A protein with C8-binding capacity could not be detected. C8bp, which was isolated from the membrane of huE, inhibited the lysis of PNH-E by C5b-9 as well as the C9 polymerization. Thus, addition of C8bp restored the species restriction in PNH-E. In conclusion, we propose that lack of C8bp might represent the defect in PNH-E type III membranes, which is responsible for their enhanced lytic susceptibility towards lysis by the late complement components.
D003185:Complement C8 / Q000276:immunology*; D003186:Complement C9 / Q000276:immunology; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology*; D004910:Erythrocyte Membrane / Q000276:immunology*; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006461:Hemolysis; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000172:deficiency*
D003185:Complement C8; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D046911:Macromolecular Substances; D008565:Membrane Proteins; D003165:Complement System Proteins