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

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.

The CD300 family of molecules are evolutionarily significant regulators of leukocyte functions

“…Functionally, internalization indicates roles in phagocytosis, antigen delivery, regulation of effector mechanisms or even viral infection. In addition to internalization, studies using transfectants have demonstrated that CD300g transcytoses bidirectionally and recycles between the cell surface and the cytoplasm to regulate lymphocyte transendothelial migration [38].…”

Triggering receptor expressed on myeloid cells receptor family modulators: a patent review

“…Based on its expression pattern, it has been proposed that modulation of TREM-4 could be therapeutic in vascular and heart disease or as a male contraceptive (72). In mice, endothelial TREM-4 has been shown to mediate lymphocyte adhesion through its immunoglobulin domain (73). …”

Expression Depression ofCD300LG-γin Human Pulmonary Carcinoma

“…(21) CD300LG has been found to be involved in lymphocyte adhesion, rolling, and TEM, which indicates that CD300LG might play important roles in antitumor effects of lymphocytes. (1,2,(4)(5)(6)(7) In the previous study, we have successfully generated a monoclonal antibody of human CD300LG-g. (9) In this study, we preliminarily explored the involvement of CD300LG in tumorigenesis, by comparing CD300LG-c expression between pulmonary carcinoma tissues and tumor-adjacent tissues at the mRNA and protein levels. Semiquantitative reverse transcription-PCR results showed that human CD300LG-c gene expression in pulmonary carcinoma tissues was dramatically lower than in tumor-adjacent tissues.…”

“…So, normally CD300LG plays an important role in immune surveillance. (2,6,7) Many studies have revealed that cytotoxic T lymphocytes (CTLs) are the main effectors in antitumor immune response. (11)(12)(13)(14) CTLs can recognize antigenic peptides presented by MHC class II molecules and specifically kill tumor cells through releasing perforin and granzyme and through induction of apoptosis of tumor cells by the FasL-fas signal pathway.…”

“…Endothelial CD300LG enhanced lymphocyte binding and mediated lymphocyte TEM through homotypic interactions between adjacent ECs, at least in vitro. (6,7) CD300LG could also bind phosphatidylserine on the surface of apoptotic cells through its Ig domain and helps to erase these apoptotic cells, indicating it might play an important role in pathogenesis of autoimmune diseases. (8) Considering both mice CD300LG and human CD300LG were widely expressed in various tissues except for immunological privileged sites, we speculated that CD300LG might play important roles in the immune response and display antitumor effects.…”