Heparin influence on the complex of serum amyloid P component and complement C4b-binding protein.
Serum amyloid P component (SAP) forms a calcium-dependent complex with C4b-binding protein (C4BP) in human serum. this study demonstrated that heparin interacted with SAP in a calcium-dependent manner and prevented formation of the SAP.C4BP complex. Furthermore, the SAP-heparin interaction interfered with SAP binding to membranes. Therefore, all three of these interactions involved similar sites on SAP, or each interaction sterically obstructed the other binding sites. In addition to heparin, SAP bound to heparan sulfate and chondroitin sulfate. In each case, a distinct multimeric species was generated. Gel filtration and sucrose density gradient ultracentrifugation suggested that heparin and heparan sulfate produced a dimer of SAP. The dimer appeared to be the most stable structure since it was not dissociated by excess heparin. While low molecular weight heparin interacted with SAP and inhibited SAP association with membranes, the SAP dimer was not detected in sucrose density gradient ultracentrifugation studies. Polybrene prevented the interaction between SAP and heparin in both a purified system and in human serum that was enriched in SAP and heparin. In contrast, Polybrene did not seem to alter the SAP.C4BP complex. While the function of the SAP.C4BP complex is unknown, it may be important for regulation of complement and/or transport of SAP to sites in the body. Dissociation of the SAP.C4BP complex by sulfated polysaccharides such as heparin may be a physiological response that could be important during tissue damage or complement activation.
Schwalbe
R A
RA
Department of Biochemistry, University of Minnesota, St. Paul 55108.
Dahlbäck
B
B
Nelsestuen
G L
GL
D002352:Carrier Proteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D002499:Centrifugation, Density Gradient; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding; D011951:Receptors, Complement / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D006025:Glycosaminoglycans; D011951:Receptors, Complement; D000683:Serum Amyloid P-Component; D006493:Heparin