Factor XI Binding to the Platelet Glycoprotein Ib-IX-V Complex Promotes Factor XI Activation by Thrombin

• Published in: The Journal of biological chemistry Vol. 277; no. 3; pp. 1662 - 1668
• Main Authors: Baglia, Frank A., Badellino, Karen O., Li, Chester Q., López, José A., Walsh, Peter N.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 18-01-2002; American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M108319200

Factor XI binds to high affinity sites on the surface of stimulated platelets where it is efficiently activated by thrombin. Here, we provide evidence that the factor XI binding site on platelets is in the glycoprotein (GP) Ibα subunit of the GP Ib-IX-V complex as follows. 1) Bernard-Soulier platelets, lacking the complex, are deficient in factor XI binding; 2) two GP Ibα ligands, SZ-2 (a monoclonal antibody) and bovine von Willebrand factor, inhibit factor XI binding to platelets; 3) by surface plasmon resonance, factor XI bound specifically to glycocalicin (the extracellular domain of GP Ibα) in Zn2+-dependent fashion (Kdapp ∼ 52 nm). We then investigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibα ligand. In the presence of high molecular weight kininogen (45 nm), Zn2+and Ca2+ ions, thrombin activated factor XI in the presence of glycocalicin at rates comparable with those seen in the presence of dextran sulfate (1 μg/ml). With higher high molecular weight kininogen concentrations (360 nm), the rate of thrombin-catalyzed factor XI activation in the presence of glycocalicin was comparable with that on activated platelets. Thus, factor XI binds to the GP Ib-IX-V complex, promoting its activation by thrombin.