β<sub>2</sub>-Glycoprotein I binds factor XI and inhibits its activation by thrombin and factor XIIa: Loss of inhibition by clipped β<sub>2</sub>-glycoprotein I

DOI Web Site 被引用文献3件
  • Tong Shi
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • G. Michael Iverson
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • Jian C. Qi
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • Keith A. Cockerill
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • Matthew D. Linnik
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • Pamela Konecny
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121
  • Steven A. Krilis
    Departments of Medicine and Immunology, Allergy, and Infectious Diseases, St. George Hospital, University of New South Wales, Kogarah 2217, Australia; and La Jolla Pharmaceutical Company, San Diego, CA 92121

抄録

<jats:p>Activation of factor XI (FXI) by thrombin<jats:italic>in vivo</jats:italic>plays a role in coagulation by providing an important positive feedback mechanism for additional thrombin generation. FXI is activated<jats:italic>in vitro</jats:italic>by thrombin, or FXIIa in the presence of dextran sulfate. In this report, we investigated the effect of β<jats:sub>2</jats:sub>-glycoprotein I (β<jats:sub>2</jats:sub>GPI) on the activation of FXI. β<jats:sub>2</jats:sub>GPI bound FXI<jats:italic>in vitro</jats:italic>and inhibited its activation to FXIa by thrombin and FXIIa. The affinity of the interaction between β<jats:sub>2</jats:sub>GPI and FXI was equivalent to the interaction between FXI and high molecular weight kininogen. Inhibition of FXI activation occurred with lower concentrations of β<jats:sub>2</jats:sub>GPI than found in human plasma. Proteolytic clipping of β<jats:sub>2</jats:sub>GPI by plasmin abolished its inhibition of FXI activation. The results suggest a mechanism of regulation whereby physiological concentrations of β<jats:sub>2</jats:sub>GPI may attenuate thrombin generation<jats:italic>in vivo</jats:italic>by inhibition of FXI activation. Plasmin cleavage of β<jats:sub>2</jats:sub>GPI provides a negative feedback that counteracts its inhibition of FXI activation.</jats:p>

収録刊行物

被引用文献 (3)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ