Histidine-rich glycoprotein (HRGP) is a multifunctional plasma protein of unclear physiologic significance. It binds not only proteins (plasminogen, fibrinogen, thrombospondin, vitronectin, immunoglobulin G, complement components) but also heparin, transition metals, and heme, and it binds to several types of cells (T-lymphocytes, macrophages, platelets). Therefore, it may be a modulator of fibrinolysis, an immunoregulator, and a carrier of trace metals. The interaction of HRGP with platelets and the ultimate effect of this interaction on platelet-dependent processes in fibrinolysis are areas of interest. A method for purifying HRGP from fresh plasma was previously developed, and more recently have been using the protein in a variety of studies. So far, several types of interaction between HRGP and platelets have been discovered: (1) HRGP binds saturably to platelets when it is liganded to a transition metal (e.g., zinc); (2) plasminogen also promotes HRGP binding to platelets, although HRGP reduces the affinity of plasminogen binding to platelets; (3) zinc-liganded HRGP augments plasminogen binding to platelets; and (4) in the presence of HRPG (with or without zinc), platelet-dependent activation of plasminogen by tissue plasminogen activator is increased. These observations suggest a complex role for HRPG in regulating fibrinolysis in a platelet-rich fibrin clot. The laboratory is also exploring the possibility of exploiting the heparin-binding capacity of HRGP on a clinical heparin antidote. The interactions of HRGP, heparin, and zinc are being studied in vitro using assays based on thrombin inhibition.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL010220-08
Application #
6431836
Study Section
Cognition and Perception Study Section (CP)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Horne 3rd, M K; Merryman, P K; Cullinane, A M (2001) Histidine-proline-rich glycoprotein binding to platelets mediated by transition metals. Thromb Haemost 85:890-5