Comparison of the activity of polyanions and polycations on the classical and alternative pathways of complement

Polyanions and polycations inhibit activity of the alternative and classical pathways of complement. We compared polyanions (commercial porcine heparin, chondroitin sulfate A, chondroitin sulfate B (dermatan sulfate), chondroitin sulfate C and heparatin sulfate) with polycations (salmon sperm protamine sulfate, poly-L-lysine, poly-L-arginine, polybrene and a synthetically prepared portion of platelet factor 4) for ability to inhibit alternative and classical pathway activity. The polyanions had considerably more activity on the alternative than on the classical pathway, whereas the polycations more profoundly inhibited classical than alternative pathway activity. For example, heparin, a polyanion, at 1.0 micrograms (7.7 x 10(-7) M based upon an Mr average of 13000)/10(7) cellular intermediates, inhibited alternative pathway activity and classical pathway activity by 77 and 14%, respectively, whereas protamine sulfate, a polycation, at 0.25 micrograms/10(7) cellular intermediates, inhibited these two pathways by 34 and 98%, respectively. These studies suggest that the capacity to inhibit complement activity is a common feature of highly charged substances and the polyanions preferentially inhibit the alternative pathway while polycations preferentially inhibit the classical pathway. In vivo these highly charged substances could play an important role in the tissues in regulating the activity of both pathways of complement.