RETRACTED: Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin.
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) Ibalpha 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 Ibalpha 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 Ibalpha) in Zn(2+)-dependent fashion (K(d)( app) approximately 52 nm). We then investigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibalpha ligand. In the presence of high molecular weight kininogen (45 nm), Zn(2+) and Ca(2+) ions, thrombin activated factor XI in the presence of glycocalicin at rates comparable with those seen in the presence of dextran sulfate (1 microg/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.
Baglia
Frank A
FA
The Sol Sherry Thrombosis Research Center and Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Badellino
Karen O
KO
Li
Chester Q
CQ
Lopez
Jose A
JA
Walsh
Peter N
PN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D002417:Cattle; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D005172:Factor XI / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011485:Protein Binding; D011869:Radioligand Assay; D020349:Surface Plasmon Resonance; D013917:Thrombin / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin; D014841:von Willebrand Factor; D005172:Factor XI; D013917:Thrombin