International Immunology Advance Access originally published online on July 12, 2004
International Immunology 2004 16(9):1265-1274; doi:10.1093/intimm/dxh128
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© 2004 The Japanese Society for Immunology
Endomucin, a sialomucin expressed in high endothelial venules, supports L-selectin-mediated rolling
1 Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
2 Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan
3 Program of Molecular Pathology, Aichi Cancer Center, Research Institute, Nagoya, 464-8681, Japan
4 Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037, USA
5 Present address: Biochemistry and Cell Biology Unit, HMRO, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan
Correspondence to: M. Miyasaka; E-mail: mmiyasak{at}orgctl.med.osaka-u.ac.jp
Lymphocyte homing to lymph nodes is regulated by transient but specific interactions between lymphocytes and high endothelial venules (HEVs), the initial phase of which is mainly governed by the leukocyte adhesion molecule L-selectin, which recognizes sulfated and sialylated O-linked oligosaccharides displayed on sialomucin core proteins. One of the sialomucin proteins, endomucin, is predominantly expressed in vascular endothelial cells of a variety of tissues including the HEVs of lymph nodes; however, whether it functions as a ligand for L-selectin remains to be formally proven. Here we show that the endomucin splice isoform a is predominantly expressed in PNAd+ HEVs and MAdCAM-1+ HEVs, as seen in non-HEV-type vascular endothelial cells. Using affinity purification with soluble L-selectin, we found that HEV endomucin is specifically modified with L-selectin-reactive oligosaccharides and can bind L-selectin as well as an HEV-specific mAb, MECA-79. Our results also indicated that a 90–100 kDa endomucin species is preferentially decorated with L-selectin-reactive sugar chains, whereas an 80 kDa species represents conventional forms expressed in non-HEV-type vascular endothelial cells in lymph nodes. Furthermore, a CHO cell line expressing endomucin together with a specific combination of carbohydrate-modifying enzymes [core-2 ß-1,6-N-acetylglucosaminyltransferase (C2GnT), 
-1,3-fucosyltransferase VII (FucTVII) and L-selectin ligand sulfotransferase (LSST)] showed L-selectin-dependent rolling under flow conditions in vitro. These results suggest that when endomucin is appropriately modified by a specific set of glycosyltransferases and a sulfotransferase, it can function as a ligand for L-selectin, and that the endomucin expressed in HEVs may represent another sialomucin ligand for L-selectin.
Keywords: carbohydrate-modifying enzymes, glycosylation, L-selectin ligand, lymphocyte homing, MECA-79
* These authors contributed equally to this work.
Transmitting editor: H. Karasuyama
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