血管内皮細胞の凝固・線溶因子発現に対する CD40 Ligand 発現 T リンパ球接着の影響 Effects of CD40 Ligand expressed T lymphocyte adhesion on coagulant and fibrinolytic activities of endothelial cells

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血管内皮細胞の凝固・線溶因子発現に対するCD40-CD40 Ligand (CD40L) 相互作用の影響を検討する目的で, 培養血管内皮細胞とCD40L発現リンパ球の接着実験を行った. IFN-γで活性化し, CD40発現を増加させた血管内皮細胞と, CD40Lを発現させた後固定したTリンパ球を共培養すると, 血管内皮細胞表面に tissue factor (TF) の強い発現が認められた. このTF発現は抗CD40L抗体で, 部分的ではあるが特異的に阻害された. また, CD40L発現Tリンパ球の接着により, 血管内皮細胞中の thrombomodulin 抗原量および培養上清中の tissue factor pathway inhibitor 抗原量は低下した. 一方, 血管内皮細胞による tissue-type plasminogen activator の産生・放出は著しく増加したが, 培養上清中には plasminogen activator inhihibitor-1が常に過剰量存在していた. 以上のことから, 炎症性免疫反応部位において血管内皮細胞に活性化Tリンパ球が接着すると, 血管内皮細胞表面は凝固亢進状態へ著しく modulate されるという結論が得られた. なお, この反応にはCD40-CD40L相互作用の関与が示唆された.

Modulation of procoagulant and fibrinolytic properties of endothelial cells mediated by adhesion with activated T lymphocytes was studied by focusing on the CD40-CD40 Ligand (CD40L) interaction. Cultured human umbilical vein endothelial cells (HUVECs) were treated with interferon-γ to increase the expression of CD40, and co-cultured with T lymphocytes that had been isolated from peripheral blood, activated with PMA and ionomycin to induce the expression of CD40L and fixed with 1% paraformaldehyde. This co-culture gave rise to the generation of tissue factor (TF) on the surface of HUVECs, but co-culture of the HUVECs with non-activated T lymphocytes failed to do so. TF expressed on the HUVECs was specifically but only partially inhibited by an anti-CD40L monoclonal antibody. By contrast, co-culture of HUVECs with the activated and fixed T lymphocytes resulted in both down-regulation of thrombomodulin in HUVECs and decrease of release of tissue factor pathway inhibitor from HUVECs. Futhermore, the co-culture enhanced the release of tissue-type plasminogen activator (t-PA) from the HUVECs without affecting the release of plasminogen activator inhibitor-1, which was still in great excess of t-PA. These results altogether suggest that the CD40-CD40L-involved adhesion of activated T lymphocytes to endothelial cells that could occur at the inflammatory sites is likely to shift the nature of endothelial cell surface toward the thrombogenic state.

収録刊行物

  • 日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis

    日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis 11(6), 531-541, 2000-12-01

    The Japanese Society on Thrombosis and Hemostasis

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各種コード

  • NII論文ID(NAID)
    10008601946
  • NII書誌ID(NCID)
    AN10353762
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    09157441
  • データ提供元
    CJP書誌  J-STAGE 
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