Tu L, Delahunty M D, Ding H, Luscinskas F W, Tedder T F
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
J Exp Med. 1999 Jan 18;189(2):241-52. doi: 10.1084/jem.189.2.241.
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.
L-选择素在炎症过程中介导白细胞在血管内皮上滚动。尽管血管内皮可被炎性细胞因子激活以表达功能性L-选择素配体,但这些配体尚未得到充分表征。在本研究中,用岩藻糖基转移酶VII cDNA(Fuc-TVII)转染EA.hy926人血管内皮细胞系(926-FtVII)可诱导功能性L-选择素配体表达以及唾液酸化路易斯x(sLex)的表达,这由HECA-452(皮肤淋巴细胞抗原;CLA)和CSLEX-1单克隆抗体所定义。人脐静脉内皮细胞(HUVEC)的细胞因子激活也可诱导功能性L-选择素配体表达,同时CLA表达增加且Fuc-TVII转录增加。用HECA-452单克隆抗体处理内皮细胞可特异性阻断大多数依赖L-选择素的淋巴细胞与活化的HUVEC和926-FtVII细胞的附着,但CSLEX-1单克隆抗体则不能。血管内皮上携带CLA的配体还需要硫酸化和合适的分子支架以发挥功能活性,但与先前由MECA-79单克隆抗体鉴定的L-选择素配体不同。这些发现表明,由HECA-452定义的抗原CLA是血管L-选择素配体的一种必需碳水化合物成分。