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

Eiji Umemoto, Toshiyuki Tanaka, Hidenobu Kanda, Soojung Jin, Kazuo Tohya, Kazuhiro Otani, Takahiro Matsutani, Masanori Matsumoto, Yukihiko Ebisuno, Ho Jang Myoung, Minoru Fukuda, Takako Hirata, Masayuki Miyasaka

Research output: Contribution to journalArticlepeer-review

Abstract

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. JEM

Original languageEnglish (US)
Pages (from-to)1603-1614
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number6
DOIs
StatePublished - Jun 12 2006
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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