Nepmucin/CLM-9, an Ig domain-containing sialomucin in vascular endothelial cells, promotes lymphocyte transendothelial migration in vitro

Jin, Soojung; Umemoto, Eiji; Tanaka, Toshiyuki; Shimomura, Yoshimitsu; Tohya, Kazuo; Kunizawa, Keiji; Yang, Bo-Gie; Jang, Myoung Ho; Hirata, Takako; Miyasaka, Masayuki

doi:10.1016/j.febslet.2008.07.041

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Volume 582, Issue 20 , Pages 3018-3024, 3 September 2008

Nepmucin/CLM-9, an Ig domain-containing sialomucin in vascular endothelial cells, promotes lymphocyte transendothelial migration in vitro

Edited by Beat Imhof

Soojung Jin
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Laboratory of Immunodynamics, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Eiji Umemoto
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Laboratory of Immunodynamics, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
- Corresponding author. Address: Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Fax: +81 6 6879 3979.
Toshiyuki Tanaka
- Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Japan
Yoshimitsu Shimomura
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Kazuo Tohya
- Department of Anatomy, Kansai University of Health Sciences, Osaka 590-0482, Japan
Keiji Kunizawa
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Laboratory of Immunodynamics, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Bo-Gie Yang
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Myoung Ho Jang
- Laboratory of Gastrointestinal Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
Takako Hirata
- Laboratory of Combined Research on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Masayuki Miyasaka
- Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
- Laboratory of Immunodynamics, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan

Received 6 June 2008; received in revised form 24 July 2008; accepted 24 July 2008. published online 01 August 2008.

Abstract

Nepmucin/CLM-9 is an Ig domain-containing sialomucin expressed in vascular endothelial cells. Here we show that, like CD31, nepmucin was localized to interendothelial contacts and to vesicle-like structures along the cell border and underwent intracellular recycling. Functional analyses showed that nepmucin mediated homotypic and heterotypic cell adhesion via its Ig domain. Nepmucin-expressing endothelial cells showed enhanced lymphocyte transendothelial migration (TEM), which was abrogated by anti-nepmucin mAbs that block either homophilic or heterophilic binding. Notably, the mAbs that inhibited homophilic binding blocked TEM without affecting lymphocyte adhesion. These results suggest that endothelial nepmucin promotes lymphocyte TEM using multiple adhesion pathways.

Abbreviations: LNs, lymph nodes, HEVs, high endothelial venules, PPs, Peyer’s patches, LBRC, lateral border recycling compartment, MBEC4, mouse brain endothelial cell 4, EC, endothelial cell, TEM, transendothelial migration