Inhibition of human and guinea pig complement by heparin fractions differing in affinity for antithrombin III or in average molecular weight.
Heparin comprises a mixture of structurally related molecules. Affinity for antithrombin III (AT III) is a prerequisite for its anticoagulant activity, which also is dependent on its molecular weight. In this study heparin fractions prepared by affinity chromatography on immobilized AT III and by gel filtration chromatography were compared for their ability to inhibit complement mediated haemolysis and both classical and alternative pathway C3 activation as measured by crossed immunoelectrophoresis. In normal human serum, inhibition of haemolysis and of heat-aggregated IgG (HAGG) as well as zymosan induced C3 activation by heparin was found to be independent of its AT III affinity and of its molecular weight (range 4800-17,000), on a weight basis. In guinea pig serum similar results were obtained for inhibition of HAGG induced C3 activation, but inhibition of haemolysis showed a marked molecular weight dependency and was also reduced for the fraction with low affinity for AT III. This may reflect a species difference in the haemolytic action of human and guinea pig complement. It is concluded that inhibition of human complement by heparin is independent of its anticoagulant activity and of its size and it is suggested that a fraction of heparin with reduced risk for bleeding and platelet aggregation is a potential anti-inflammatory agent.
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D003176:Complement C3 / Q000037:antagonists & inhibitors*; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D006168:Guinea Pigs; D006461:Hemolysis / Q000187:drug effects; D006493:Heparin / Q000032:analysis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D011485:Protein Binding
D003176:Complement C3; D000990:Antithrombin III; D006493:Heparin