The cutaneous lymphocyte antigen is an essential component of the L-selectin ligand induced on human vascular endothelial cells.

The cutaneous lymphocyte antigen is an essential component of the L-selectin ligand induced on human vascular endothelial cells.
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DOI:
10.1084/jem.189.2.241
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发表时间:
1999-01-18
影响因子:
15.3
通讯作者:
Tedder, T F
Tedder, T F
中科院分区:
医学1区
文献类型:
--
作者:
Tu, L;Delahunty, M D;Ding, H;Luscinskas, F W;Tedder, T F

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炎症过程中l -选择素介导白细胞在血管内皮上的滚动。虽然血管内皮可以被炎症细胞因子激活来表达功能性的l -选择素配体,但这些配体尚未被很好地表征。在本研究中,转染EA.hy926人血管内皮细胞系(926-FtVII)的focusyltransferase VII cDNA (Fuc-TVII)诱导了功能性l -选择素配体的表达和sialyl Lewisx (sLex)的表达,由HECA-452(皮肤淋巴细胞抗原;CLA)和CSLEX-1单克隆抗体定义。人脐静脉内皮细胞(HUVEC)的细胞因子激活也诱导了功能性l -选择素配体的表达,CLA表达和Fuc-TVII转录增加。大多数l -选择素依赖的淋巴细胞附着在活化的HUVEC和926-FtVII细胞上,被hea -452单抗特异性阻断,而CSLEX-1单抗不能。血管内皮上的含cla的配体也需要硫酸酸化和适当的分子支架来维持功能活性,但与MECA-79 mAb先前鉴定的l -选择素配体不同。这些发现表明,HECA-452定义的抗原CLA是血管l -选择素配体的重要碳水化合物成分。
L-selectin mediates leukocyte rolling on vascular endothelium during inflammation. Although vascular endothelium can be activated with inflammatory cytokines to express functional L-selectin ligands, these ligands have not been well characterized. In this study, fucosyltransferase VII cDNA (Fuc-TVII) transfection of the EA.hy926 human vascular endothelial cell line (926-FtVII) induced functional L-selectin ligand expression and expression of sialyl Lewisx (sLex), as defined by HECA-452 (cutaneous lymphocyte antigen; CLA) and CSLEX-1 mAbs. Cytokine activation of human umbilical vein endothelial cells (HUVEC) also induced functional L-selectin ligand expression, with increased CLA expression and Fuc-TVII transcription. The majority of L-selectin–dependent lymphocyte attachment to activated HUVEC and 926-FtVII cells was blocked specifically by treating the endothelial cells with the HECA-452 mAb, but not the CSLEX-1 mAb. CLA-bearing ligands on vascular endothelium also required sulfation and appropriate molecular scaffolds for functional activity, but were distinct from the L-selectin ligands previously identified by the MECA-79 mAb. These findings demonstrate that the HECA-452– defined antigen, CLA, is an essential carbohydrate component of vascular L-selectin ligands.