Modulation of the formation of the amplification convertase of complement, C3b, Bb, by native and commercial heparin.
Native rat mast cell macromolecular heparin proteoglycan and commercial hog heparin glycosaminoglycan chains inhibit generation of the amplification convertase, C3b, Bb. The inhibitory action of heparin is not due to chelation of magnesium. Heparin is most active in inhibiting convertase formation on cellular intermediates formed with the lowest C3b input and developed with the highest B concentration, thereby suggesting the receptor site for B on C3b as the point of heparin action. This interpretation is consistent with the demonstration that heparin prevents B utilization during the fluid phase interaction of C3b, B, and D. Inhibition is observed also when C3b,Bb generation takes place on cellular intermediates in the presence of P or C3NeF, which yield stabilized forms of the convertase. 50 times the concentration of heparin required to inhibit convertase generation does not accelerate the decay of the unstabilized or the C3NeF-stabilized convertases and has only a modest effect on the P-stabilized convertase. An additional effect of heparin is to impair beta1H-mediated decay-dissociation of C3b,Bb. The concentration of native or commercial heparin which prevents convertase formation is in the same range as that required for the demonstration of its anti-coagulant and anti-thrombin III cofactor activities. The additional finding that this inhibitory action of heparin can be expressed by the isolated mast cell granule suggests that native heparin may contribute to the modulation of the amplification pathway of complement.
D000818:Animals; D003166:Complement Activating Enzymes / Q000037:antagonists & inhibitors*; D050577:Complement C3-C5 Convertases / Q000037:antagonists & inhibitors*; D003180:Complement C3b Inactivator Proteins; D011415:Complement Factor B / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D007700:Kinetics; D008407:Mast Cells / Q000276:immunology; D008970:Molecular Weight; D051381:Rats; D013329:Structure-Activity Relationship
D003180:Complement C3b Inactivator Proteins; D006493:Heparin; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases; D011415:Complement Factor B