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(Circulation. 2003;108:623.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Glycosyl Phosphatidylinositol Anchorage of Tissue Factor Pathway Inhibitor

Jing Zhang, PhD; Orlando Piro, MD; Lan Lu; George J. Broze, Jr, MD

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

Correspondence to George J. Broze, Jr, MD, BJH 90-20-66, 216 South Kingshighway Blvd, St Louis, MO 63110. E-mail gbroze{at}im.wustl.edu

Received January 30, 2003; revision received April 7, 2003; accepted April 19, 2003.

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 TFPIß/TFPI mRNA of 0.1 to 0.2. In Chinese hamster ovary (CHO) cells, TFPI is predominantly secreted, whereas TFPIß is a GPI-anchored membrane protein. Like TFPIß, 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 (TFPIß) 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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