Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins.
Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity.
Sakai
T
T
Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131.
Kisiel
W
W
D001051:Apoenzymes / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D008074:Lipoproteins / Q000097:blood* / Q000302:isolation & purification; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*
D001051:Apoenzymes; C052493:F3 protein, human; D007457:Iodine Radioisotopes; D008074:Lipoproteins; D011994:Recombinant Proteins; D013925:Thromboplastin