Heparin prevents formation of the human C3 amplification convertase by inhibiting the binding site for B on C3b.
Fluid-phase heparin prevents generation of the C3 amplification convertase of human complement, C3b, Bb most likely by inhibiting the formation of the bimolecular complex between cell-bound C3b and B. The effect of heparin on the binding of B to C3b was examined using 125I-labelled B and C3b-bearing sheep erythrocytes (EsC3b). In the absence of heparin, B bound to EsC3b with an affinity of 0.5-1 X 10(6) M-1 in the presence of 5 mM Mg2+. Incremental amounts of heparin (100-700 micrograms/10(7) EsC3b) inhibited the binding of 125I-B to C3b in a dose-dependent manner. Scatchard analysis of the binding data in the presence of four inhibitory concns of heparin revealed that heparin did not affect the binding affinity of B for C3b but decreased the number of C3b sites recognized by B on the cells. No inhibition of binding occurred in the presence of totally (N- and O-) desulfated heparin which has no anticomplementary activity. These results demonstrate that heparin prevents generation of the C3 amplification convertase by binding to cell-bound C3b and masking the binding site for B on C3b.
D000818:Animals; D001665:Binding Sites; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors*; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors*; D003179:Complement C3b / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D012756:Sheep
D004792:Enzyme Precursors; D003179:Complement C3b; D006493:Heparin; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B