Factor XI Assembly and Activation on Human Umbilical Vein Endothelial Cells in Culture

Summary

Biotin-FXI optimally bound to HUVEC in the presence of 40 nM high molecular weight kininogen (HK) and ≥ ≥7 μM Zn²⁺. There was little specific FXI binding in the absence of added HK and at concentrations of Zn²⁺ <15 μM. FXI and prekallikrein, but not prothrombin, blocked biotin-FXI binding to HUVEC in the presence of HK with an IC₅₀ of 18 nM and 180 nM, respectively. Monoclonal antibody HKL16 and peptide SDD31 also inhibited biotin-XI binding in the presence of HK with an IC₅₀ of 4.7 nM and 50 μM, respectively. Alternatively, peptide T²⁴⁹-F²⁶⁰ of FXI’s apple domain 3 and heparin monosulfate were weak inhibitors of FXI binding to HUVEC. FXI bound to HUVEC with an apparent K _d of 6.9 ± 3.0 nM and B _max of 13 ± 2.610⁶ sites/cell. FXI bound to HK on HUVEC, but not prothrombin, became converted to FXIa. FXI activation on HUVEC resulted from tissue culture media bovine factor XIIa. HUVEC grown in human factor XII-deficient serum did not support FXI activation. FXI binding to HUVEC in culture was mostly mediated by HK and FXI activation on HUVEC is dependent on cell-associated factor XIIa.

Keywords

Factor XI - high molecular weight kininogen - factor XII - prekallikrein - prothrombin

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