Nepmucin, a novel HEV sialomucin, mediates L-selectin–dependent lymphocyte rolling and promotes lymphocyte adhesion under flow

• Eiji Umemoto

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Toshiyuki Tanaka

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Hidenobu Kanda

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Soojung Jin

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Kazuo Tohya

  3Department of Anatomy, Kansai College of Oriental Medicine, Osaka 590-0482, Japan

• Kazuhiro Otani

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Takahiro Matsutani

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Masanori Matsumoto

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Yukihiko Ebisuno

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Myoung Ho Jang

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

• Minoru Fukuda

  4Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, CA 92037

• Takako Hirata

  2The 21st Century Center of Excellence Program, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

• Masayuki Miyasaka

  1Laboratory of Immunodynamics, Department of Microbiology and Immunology, Graduate School of Medicine

抄録

Lymphocyte trafficking to lymph nodes (LNs) is initiated by the interaction between lymphocyte L-selectin and certain sialomucins, collectively termed peripheral node addressin (PNAd), carrying specific carbohydrates expressed by LN high endothelial venules (HEVs). Here, we identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches [PPs]), that is expressed in LN HEVs but not detectable in PP HEVs at the protein level. Unlike conventional sialomucins, nepmucin contains a single V-type immunoglobulin (Ig) domain and a mucin-like domain. Using materials affinity-purified from LN lysates with soluble L-selectin, we found that two higher molecular weight species of nepmucin (75 and 95 kD) were decorated with oligosaccharides that bind L-selectin as well as an HEV-specific MECA-79 monoclonal antibody. Electron microscopic analysis showed that nepmucin accumulates in the extended luminal microvillus processes of LN HEVs. Upon appropriate glycosylation, nepmucin supported lymphocyte rolling via its mucin-like domain under physiological flow conditions. Furthermore, unlike most other sialomucins, nepmucin bound lymphocytes via its Ig domain, apparently independently of lymphocyte function–associated antigen 1 and very late antigen 4, and promoted shear-resistant lymphocyte binding in combination with intercellular adhesion molecule 1. Collectively, these results suggest that nepmucin may serve as a dual-functioning PNAd in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains.

収録刊行物

• The Journal of Experimental Medicine

  The Journal of Experimental Medicine 203 (6), 1603-1614, 2006-06-05

  Rockefeller University Press

キーワード

• Immunology
• Immunology and Allergy

詳細情報

• CRID: 1362262945946970496
• NII論文ID: 30017434671
• DOI: 10.1084/jem.20052543
• ISSN: 15409538
• ISSN: 00221007
• ISSN: http://id.crossref.org/issn/00221007
• Web Site: https://rupress.org/jem/article-pdf/203/6/1603/1723712/1603.pdf
• データソース種別:
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  • CiNii Articles
  • KAKEN