Interference of propamidine with binding of the fifth component of complement to surface-fixed C3b, and with C5 activation.
The effects of propamidine and their dose dependency, on utilization of the third and fifth complement components in immune haemolysis have been compared. While C3 utilization is not disturbed that of C5 is markedly inhibited by propamidine in concentrations as low as 0.5 mM. Both, binding of C5 to surface-fixed C3b and cleavage of C5 by convertases C42 and C3bBb, are also inhibited in the presence of propamidine. Since neither C3 cleavage by these enzymes nor even C5 cleavage by the cobra venom factor-supported convertase CFVBb is significantly reduced a general convertase-inhibiting effect of propamidine is ruled out. Rather the effect on utilization of C5 is the result of interference with binding of C5 is the result of interference with binding of C5 to C3b and hence impairment of its accessibility to the convertases. These findings thus further support the role of surface fixed C3b in C5 activation proposed earlier.
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D011415:Complement Factor B; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006801:Humans
D000578:Amidines; D003176:Complement C3; D003182:Complement C5; D003179:Complement C3b; D011415:Complement Factor B