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In vivo evidence of intravascular binding sites for coagulation factor IX
Author(s) -
Stern David M.,
Knitter Glen,
Kisiel Walt,
Nawroth Peter P.
Publication year - 1987
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1987.tb01303.x
Subject(s) - factor ix , factor ixa , tissue factor , factor x , chemistry , in vivo , clotting factor , coagulation , factor vii , microbiology and biotechnology , medicine , immunology , biophysics , endocrinology , thrombin , biochemistry , biology , platelet
Summary 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 of 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 125 I‐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. 125 I‐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.