Serum amyloid P component (SAP) is a major vertebrate plasma protein of unknown function. It is a component of all known types of amyloid deposits, but its role in the pathogenesis of the amyloidoses is unknown. It is a component of normal connective tissue, but its function there is also unknown. The goals of this project are: 1) to learn more about the physiologic role(s) of SAP and 2) to learn more about the role of SAP in the pathogenesis of systemic amyloidosis. SAP will be characterized biochemically and biophysically, and studies designed to test several hypotheses regarding its physiologic function and pathophysiologic significance will be carried out. Calcium binding to SAP will be studied using equilibrium dialysis, and the effects of several chemical modifications of the protein will be determined. The aggregation of SAP and several modified derivatives by calcium will be studied using light scattering techniques. Binding of SAP to other plasma proteins and cell matrix components will be studied using a solid phase binding assay. The effect of SAP on thrombin activity and fibrin polymerization will be studied, and the incorporation of SAP into fibrin clots will be measured under various conditions. The effect of SAP on the proteolysis of fibronectin in solution and bound to a surface will be determined, as will the effect of SAP on plasminolysis of fibrin clots. SAP and fibronectin will be localized in the matrix of cultured fibroblasts using a double immunofluorescent labeling technique. Serum from patients with systemic amyloidosis will be studied to detect any abnormal SAP-binding proteins present, and the effect of such serum on the deposition of SAP in the matrix of cultured fibroblasts will be determined.
| Meyer, K; Smith, R; Williams, E C (1987) Inhibition of fibrin polymerization by serum amyloid P component and heparin. Thromb Haemost 57:345-8 |
