Serum amyloid p component does not circulate in complex with C4-binding protein, fibronectin or any other major protein ligand.

Serum amyloid P component (SAP) is a pentameric plasma protein associated with all known kinds of amyloid. The normal physiological function of the protein has not been fully elucidated but it may be involved in clearance of cellular debris and in innate immunity. An important clue to its normal function is the identity of ligands bound to SAP in the circulation. It has been reported that all SAP is complexed with C4-binding protein (C4bp) but other studies have not been able to confirm this. We here study this issue by a combination of crossed immunoelectrophoresis (CIE), size exclusion chromatography, and native polyacrylamide electrophoresis and we show that SAP in serum – analysed under native analysis conditions and free of immobilizing antibodies – does not have any major protein ligand. However, when the protein is aggregated by immobilized antibodies, C4bp and fibronectin clearly bind to SAP. If circulating SAP under normal circumstances bind any protein ligand in vivo, our results strongly suggest that this only occurs to a minor extent.