The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/1/241/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 2, January 18, 1999 241-252

Articles

The Cutaneous Lymphocyte Antigen Is an Essential Component of the L-selectin Ligand Induced on Human Vascular Endothelial Cells

LiLi Tu*, Martha D. Delahunty*, Han Ding{ddagger}, Francis W. Luscinskas{ddagger}, and Thomas F. Tedder*

From the * Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710; and {ddagger} Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02160

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.

Key Words: L-selectin • cutaneous lymphocyte antigen • endothelium • human leukocytes • adhesion

Address correspondence to Thomas F. Tedder, Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710. Phone: 919-684-3578; Fax: 919-684-8982; E-mail: tedde003{at}mc.duke.edu

L. Tu and M.D. Delahunty contributed equally to this work.

1 Abbreviations used in this paper: CLA, cutaneous lymphocyte antigen; Fuc-TVII, fucosyltransferase-VII; 926-FtVII, EA.hy926 cells stably transfected with Fuc-TVII cDNA; HEV, high endothelial venules; HUVEC, human umbilical vein endothelial cells; L'IgM, human L-selectin–mouse IgM fusion protein; OSGE, O-sialoglycoprotease; PSGL-1, P-selectin glycoprotein ligand-1; sLex, sialyl Lewisx.


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