Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells
Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells
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DOI：
10.4049/jimmunol.169.2.983
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发表时间：
2002-07-15
影响因子：
4.4
通讯作者：
Adams, DH
中科院分区：
文献类型：
--
作者：
Lalor, PF;Edwards, S;Adams, DH
血管粘附蛋白-1（VAP-1）是一种由人肝脏内皮细胞表达的胺氧化酶和粘附受体。肝窦由低流速的血液灌注，窦内皮缺乏选择素表达，并且具有低水平的CD 31，这表明VAP-1可能在淋巴细胞募集到肝脏中发挥特定作用。为了支持这一点，我们现在报告VAP-1的组成型表达的人肝窦内皮细胞（HSEC）在体外，并证明VAP-1支持粘附和迁移的淋巴细胞在这些细胞在生理剪切应力。这些是首次报道VAP-1对原代人内皮细胞的功能的研究。在静态条件下，淋巴细胞与未刺激的HSEC的粘附依赖于VAP-1和ICAM-2，而与TNF-α刺激的HSEC的粘附依赖于ICAM-1、VCAM-1和VAP-1。在流动的条件下，阻断VAP-1使淋巴细胞与TNF-α处理的HSEC的粘附减少了50%，并显著降低了穿过细胞因子或LPS激活的内皮的粘附淋巴细胞的比例。此外，VAP-1的胺氧化酶活性的抑制将淋巴细胞的粘附和迁移降低到与VAP-1 Ab相似的水平。因此，VAP-1可以支持跨内皮迁移以及粘附，并且这两种功能都依赖于其酶活性。在缺乏选择素和CD 31的情况下，VAP-1可能通过肝窦内皮在淋巴细胞募集中发挥特异性作用。此外，由于VAP-1在非内皮细胞内皮上响应于炎症而被诱导，因此其支持淋巴细胞跨内皮迁移的能力可能是VAP-1的重要系统功能。
Vascular adhesion protein-1 (VAP-1) is an amine oxidase and adhesion receptor that is expressed by endothelium in the human liver. The hepatic sinusoids are perfused by blood at low flow rates, and sinusoidal endothelium lacks selectin expression and has low levels of CD31, suggesting that VAP-1 may play a specific role in lymphocyte recruitment to the liver. In support of this we now report the constitutive expression of VAP-1 on human hepatic sinusoidal endothelial cells (HSEC) in vitro and demonstrate that VAP-1 supports adhesion and transmigration of lymphocytes across these cells under physiological shear stress. These are the first studies to report the function of VAP-1 on primary human endothelial cells. Under static conditions lymphocyte adhesion to unstimulated HSEC was dependent on VAP-1 and ICAM-2, whereas adhesion to TNF-alpha-stimulated HSEC was dependent on ICAM-1, VCAM-1, and VAP-1. Under conditions of flow, blocking VAP-1 reduced lymphocyte adhesion to TNF-alpha-treated HSEC by 50% and significantly reduced the proportion of adherent lymphocytes that transmigrated across cytokine or LPS-activated endothelium. In addition, inhibition of the amine oxidase activity of VAP-1 reduced both adhesion and transmigration of lymphocytes to a level similar to that seen with VAP-1 Ab. Thus, VAP-1 can support transendothelial migration as well as adhesion, and both functions are dependent on its enzymatic activity. In the absence of selectins and CD31, VAP-1 may play a specific role in lymphocyte recruitment via hepatic sinusoidal endothelium. Moreover, since VAP-1 is induced on nonbepatic endothelium in response to inflammation, its ability to support lymphocyte transendothelial migration may be an important systemic function of VAP-1.