Full-length human tissue factor pathway inhibitor inhibits human activated protein C in the presence of heparin.
Previous studies have demonstrated that tissue factor pathway inhibitor (TFPI) purified from a hepatoma cell line failed to inhibit human activated protein C (APC) or human thrombin. In the present study, we have examined the ability of full-length TFPI and a truncated form of TFPI lacking the third Kunitz-type domain and C-terminal tail (TFPI1-161) to inhibit the amidolytic activity of human APC in the presence and absence of heparin. TFPI readily inhibited APC amidolytic activity only in the presence of heparin, whereas TFPI1-161 failed to inhibit APC amidolytic activity in the presence or absence of heparin. Optimal inhibition of APC by TFPI was observed at 1 U/ml heparin. The results of competition studies between factor Xa and APC for inhibition by TFPI in the presence of heparin suggested that the second Kunitz-type domain in TFPI was responsible for the inhibition of APC.
Hamamoto
T
T
Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
Kisiel
W
W
D000925:Anticoagulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D011486:Protein C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000925:Anticoagulants; D008074:Lipoproteins; D011486:Protein C; D015842:Serine Proteinase Inhibitors; C051928:lipoprotein-associated coagulation inhibitor; D006493:Heparin