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Nepmucin/CLM-9, an Ig domain-containing sialomucin in vascular endothelial cells, promotes lymphocyte transendothelial migration in vitro
Authors:Jin Soojung  Umemoto Eiji  Tanaka Toshiyuki  Shimomura Yoshimitsu  Tohya Kazuo  Kunizawa Keiji  Yang Bo-Gie  Jang Myoung Ho  Hirata Takako  Miyasaka Masayuki
Institution:a Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
b Laboratory of Immunodynamics, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
c Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Japan
d Department of Anatomy, Kansai University of Health Sciences, Osaka 590-0482, Japan
e Laboratory of Gastrointestinal Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan
f Laboratory of Combined Research on Microbiology and Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
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.
Keywords:LNs  lymph nodes  HEVs  high endothelial venules  PPs  Peyer&rsquo  s patches  LBRC  lateral border recycling compartment  MBEC4  mouse brain endothelial cell 4  EC  endothelial cell  TEM  transendothelial migration
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