Surface-dependent modulation by H of C5 cleavage by the cell-bound alternative pathway C5 convertase of human complement.
Regulation by H of formation of the C3 and C5 alternative pathway convertases of complement on cells is dependent on such chemical characteristics of the cell surfaces as their membrane content in sialic acid. Properdin-stabilized C5 convertase sites were assembled on the non-activating cells of the alternative pathway, sheep erythrocytes (Es), and on the activating cells, desialated Es and rabbit erythrocytes (Er). C5 hemolytic sites were revealed by incubation of the convertase-bearing cells with limiting C5 and excess C6-C9. H inhibited generation of C5 hemolytic sites in a dose-related fashion on Es, Er, and desialated Es at molar ratios of H/C5 of 0.03 to 0.5. H similarly inhibited C5 utilization by the cell-bound C5 convertase on Es and desialated Es regardless of the cell membrane sialic acid content; however, H was three to five times less effective on Er. Kinetic experiments also suggested that C5 hemolytic sites are generated more rapidly on Er than on Es and desialated Es. The inhibition effect of H was independent of the number of C5 convertase sites per cell on all cell types; two to three times more residual hemolytic sites were found on convertase-bearing Es that had been incubated with C5 and H as compared with cells that had been decayed by H before incubation with C5. Furthermore, H also inhibited C5 interaction with a preformed classical pathway C5 convertase. These results suggest that H interacts with C5 so as to alter C5 binding and/or cleavage by the cell-bound C5 alternative pathway convertase. Sialic acid-independent modulation by H of C5 cleavage by the C5 convertase represents an additional regulatory step in the activation of the human alternative complement pathway.
D000818:Animals; D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000096:biosynthesis / Q000378:metabolism*; D003167:Complement Activation; D003180:Complement C3b Inactivator Proteins / Q000502:physiology*; D003182:Complement C5 / Q000378:metabolism*; D017242:Complement Factor H; D003170:Complement Pathway, Alternative; D004910:Erythrocyte Membrane / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D011817:Rabbits; D012756:Sheep
C493495:CFH protein, human; D003180:Complement C3b Inactivator Proteins; D003182:Complement C5; D017242:Complement Factor H; D003166:Complement Activating Enzymes