Comparison of binding characteristics of factors B and H to C3b on normal and paroxysmal nocturnal hemoglobinuria erythrocytes.
To determine if aberrant interactions of the endogenous control proteins with cell-bound C3b contribute to the greater fixation of C3b to paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes when whole serum complement is activated, we compared the characteristics of binding of factors B and H to normal and PNH red cells bearing C3b (EC3b). Factor B binding is homogeneous, there is 1:1 stoichiometry, and the affinity constant at equilibrium for factor B binding is the same for normal and PNH EC3b. In contrast, analysis by Scatchard's method of factor H binding results in a curvilinear plot, the deviation from linearity being exaggerated for the PNH EC3b. The heterogeneity of binding of factor H appears to be a consequence of the nonrandom distribution of C3b about the alternative pathway convertase site. This nonrandom distribution does not induce negative cooperativity but rather effects a biophysical milieu which enhances factor H binding. The greater heterogeneity of binding of factor H to PNH E bearing nonrandomly distributed C3b appears to be due to the presence of a greater proportion of lower affinity binding sites on the PNH EC3b. However, it appears unlikely that this greater heterogeneity of factor H binding contributes to the enhanced fixation of C3b to PNH erythrocytes.
D001667:Binding, Competitive; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D004792:Enzyme Precursors / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology*; D006801:Humans; D011951:Receptors, Complement / Q000032:analysis*; D017463:Receptors, Complement 3b
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D004792:Enzyme Precursors; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017242:Complement Factor H; D011415:Complement Factor B