Identification of multiple sites of interaction between heparin and the complement system.
Many diverse effects of heparin on the complement system have been reported. In only a few cases have the sites or the mechanisms of these effects been identified. In order to understand these results we sought to comprehensively analyze which complement proteins interact with heparin and which do not. Purified components of the classical, alternative and terminal pathways of complement were radiolabeled and their affinity for heparin determined. Affinity chromatography of normal human serum on heparin-agarose allowed a complete analysis of complement proteins and confirmed the results obtained with radiolabeled purified components. Of the 22 complement proteins examined, 13 bound heparin (C1q, C2, C4, C4bp, C1INH, B, D, H, P, C6, C8, C9, and vitronectin) while 9 did not bind heparin (C1r, C1s, C3, Factor I, C5, C7, C3b, Ba and Bb). These observations help explain the many effects heparin has on the complement system and they identify the proteins which need to be examined in order to explain these effects.
Sahu
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Department of Biochemistry, University of Texas Health Science Center, Tyler 75710.
Pangburn
M K
MK
D002846:Chromatography, Affinity; D011416:Complement Factor D / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D011485:Protein Binding
C493495:CFH protein, human; D017242:Complement Factor H; D006493:Heparin; D003165:Complement System Proteins; C493488:CFD protein, human; D011416:Complement Factor D