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 we have been using the protein in a variety of studies. So far we have established that HRGP binds saturably to platelets when it is liganded to a transition metal (e.g., zinc) and that this binding is completely blocked by a monoclonal antibody to CD36. Individuals lacking CD36 on their platelets are being sought to confirm the observation that HRG/zinc binds to CD36. We have also demonstrated that the addition of HRGP and zinc to normal plasma can inhibit clinically relevant concentrations of heparin, suggesting that HRGP plus zinc might be useful as a heparin antidote.
| 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 |
