IDENTIFICATION OF MULTIPLE SITES OF INTERACTION BETWEEN HEPARIN AND THE COMPLEMENT-SYSTEM

Many diverse effects of heparin on the complement system have been rep orted. In only a few cases have the sites or the mechanisms of these e ffects been identified. In order to understand these results we sought to comprehensively analyze which complement proteins interact with he parin and which do not. Purified components of the classical, alternat ive and terminal pathways of complement were radiolabeled and their af finity for heparin determined. Affinity chromatography of normal human serum on heparin-agarose allowed a complete analysis of complement pr oteins and confirmed the results obtained with radiolabeled purified c omponents. Of the 22 complement proteins examined, 13 bound heparin (C lq, C2, C4, C4bp, ClINH, B, D, H, P, C6, C8, C9, and vitronectin) whil e 9 did not bind heparin (Clr, Cls, C3, Factor I, C5, C7, C3b, Ba and Bb). These observations help explain the many effects heparin has on t he complement system and they identify the proteins which need to be e xamined in order to explain these effects.