Published Online
on June 30, 2003

A more recent version of this article appeared on August 5, 2003

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Submitted on January 30, 2003
Revised on April 7, 2003
Accepted on April 19, 2003

Glycosyl Phosphatidylinositol Anchorage of Tissue Factor Pathway Inhibitor

Jing Zhang PhD, Orlando Piro MD, Lan Lu , and George J. Broze Jr MD^*

From the Division of Hematology, Barnes-Jewish Hospital at Washington University Medical Center, St Louis, Mo.

^* To whom correspondence should be addressed. E-mail: gbroze{at}im.wustl.edu.

Background--The endothelium is a major source of tissue factor pathway inhibitor (TFPI), the endogenous regulator of TF-induced coagulation, and a significant proportion of the expressed TFPI remains associated with the endothelial surface.

Methods and Results--Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment reduced TFPI at the surface of cultured endothelial cells by 80%, and at least a portion of the TFPI released by PI-PLC contained an intrinsic glycosylphosphatidylinositol (GPI) anchor that is recognized by anti-crossreactive determinant antibodies. Endothelial cells express both of the alternatively spliced forms of TFPI mRNA at a ratio of TFPI/TFPI mRNA of 0.1 to 0.2. In Chinese hamster ovary (CHO) cells, TFPI is predominantly secreted, whereas TFPI is a GPI-anchored membrane protein. Like TFPI, the small proportion of the TFPI expressed by CHO cells that remains surface associated is also released by PI-PLC treatment, suggesting that it is bound to a separate GPI-anchored protein(s) at the surface of the cells.

Conclusions--Both direct (TFPI) and indirect (TFPI) GPI-mediated membrane anchorage is involved in localizing TFPI to the surface of cells.

Key words: coagulation • inhibitors • endothelium-derived factors

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