Glycoforms of human endothelial CD34 that bind L-selectin carry sulfated sialyl Lewis x capped O- and N-glycans
- 16 July 2009
- journal article
- Published by American Society of Hematology in Blood
- Vol. 114 (3), 733-741
- https://doi.org/10.1182/blood-2009-03-210237
Abstract
Endothelial sialomucin CD34 functions as an L-selectin ligand mediating lymphocyte extravasation only when properly glycosylated to express a sulfated carbohydrate epitope, 6-sulfo sialyl Lewis x (6-sulfo SLex). It is thought that multivalent 6-sulfo SLex expression promotes high-affinity binding to L-selectin by enhancing avidity. However, the reported low amount of 6-sulfo SLex in total human CD34 is inconsistent with this model and prompted us to re-evaluate CD34 glycosylation. We separated CD34 into 2 glycoforms, the L-selectin–binding and nonbinding glycoforms, L-B-CD34 and L-NB-CD34, respectively, and analyzed released O- and N-glycans from both forms. L-B-CD34 is relatively minor compared with L-NB-CD34 and represented less than 10% of total tonsillar CD34. MECA-79, a mAb to sulfated core-1 O-glycans, bound exclusively to L-B-CD34 and this form contained all sulfated and fucosylated O-glycans. 6-Sulfo SLex epitopes occur on core-2 and extended core-1 O-glycans with approximately 20% of total L-B-CD34 O-glycans expressing 6-sulfo SLex. N-glycans containing potential 6-sulfo SLex epitopes were also present in L-B-CD34, but their removal did not abolish binding to L-selectin. Thus, a minor glycoform of CD34 carries relatively abundant 6-sulfo SLex epitopes on O-glycans that are important for its recognition by L-selectin.This publication has 43 references indexed in Scilit:
- Replacing a Lectin Domain Residue in L-selectin Enhances Binding to P-selectin Glycoprotein Ligand-1 but Not to 6-Sulfo-sialyl Lewis xOnline Journal of Public Health Informatics, 2008
- Nepmucin, a novel HEV sialomucin, mediates L-selectin–dependent lymphocyte rolling and promotes lymphocyte adhesion under flowThe Journal of Experimental Medicine, 2006
- N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venulesNature Immunology, 2005
- A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venulesNature Immunology, 2005
- Core 2 Branching β1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte HomingOnline Journal of Public Health Informatics, 2004
- Sialyl-LewisxSequence 6-O-Sulfated atN-Acetylglucosamine Rather Than at Galactose Is the Preferred Ligand forl-Selectin and De-N-acetylation of the Sialic Acid Enhances the Binding StrengthBiochemical and Biophysical Research Communications, 1997
- Sulfated Sialyl Lewis X, the Putative L-Selectin Ligand, Detected on Endothelial Cells of High Endothelial Venules by a Distinct Set of Anti-Sialyl Lewis X AntibodiesBiochemical and Biophysical Research Communications, 1997
- Sialomucin CD34 is the major L-selectin ligand in human tonsil high endothelial venules.The Journal of cell biology, 1995
- The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor.The Journal of cell biology, 1991
- Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes.The Journal of cell biology, 1988