In vivo evidence of intravascular binding sites for coagulation factor IX

Abstract

Previous studies have demonstrated that factors IX/IXa bind to specific sites on the surfaces of cultured and native endothelium in vitro and that these sites should be occupied with factor IX in homeostasis. Since factor IX or different species binds to endothelium in a similar manner, we examined if infusion of heterologous factor IX into an animal should result in displacement of host factor IX antigen from its vessel wall site. Experiments were carried out in baboons with a large excess of bovine factor IX employing species-specific radioimmunoassays. The results indicate that infusion of bovine factor IX or active site-blocked factor IXa, but not prothrombin, resulted in a dose-dependent rise in the plasma level of baboon factor IX antigen. This suggested that the infused factor IX was displacing the host clotting factor from some reservoir easily accessible to the intravascular space. Consistent with this hypothesis, infusion of 125I-factor IX demonstrated accumulation in multiple organs. Radioiodinated factor IX comigrating with the initial tracer on SDS-PAGE could be eluted from the luminal surface of pulmonary artery and aortic segments. 125I-factor IX was not significantly associated with cellular elements of the blood. These results suggest that there is a pool of non-circulating factor IX which is accessible to the intravascular space, widely distributed and involves endothelium.