Recombinant full-length tissue factor pathway inhibitor fails to bind to the cell surface: Implications for catabolism in vitro and in vivo

Guyu Ho, Masaaki Narita, George J. Broze, Alan L. Schwartz

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Tissue factor pathway inhibitor (TFPI) plays a key role in the regulation of tissue factor-initiated blood coagulation secondary to loss of the integrity of the blood vessel wall. TFPI is a naturally occurring Kunitz- type protease inhibitor that inhibits coagulation factor Xa and, in a factor Xa-dependent manner, mediates feedback inhibition of the factor VIIa/tissuefactor catalytic complex. In vivo full-length TFPI is thought to be primarily bound to the vascular endothelium and the high affinity binding requires an intact carboxy terminus. Here we describe a full-length TFPI molecule, expressed in mouse C127 cells (TFPI(C127)), which exhibits virtually no cellular binding yet contains the intact carboxy terminus. This TFPI (TFPI(C127)) is neither internalized nor degraded via the TFPI endocytic receptor, LDL-receptor-related protein. Pharmacokinetic studies of TFPI(C127) in vivo demonstrate a 10-fold prolongation in the plasma half-life, compared with that of bacterial recombinant TFPI. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1973-1978
Number of pages6
JournalBlood
Volume95
Issue number6
StatePublished - Mar 15 2000

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