Endomucin prevents leukocyte–endothelial cell adhesion and has a critical role under resting and inflammatory conditions

Abstract

Endomucin is a membrane-bound glycoprotein expressed luminally by endothelial cells that line postcapillary venules, a primary site of leukocyte recruitment during inflammation. Here we show that endomucin abrogation on quiescent endothelial cells enables neutrophils to adhere firmly, via LFA-1-mediated binding to ICAM-1 constitutively expressed by endothelial cells. Moreover, TNF-α stimulation downregulates cell surface expression of endomucin concurrent with increased expression of adhesion molecules. Adenovirus-mediated expression of endomucin under inflammatory conditions prevents neutrophil adhesion in vitro and reduces the infiltration of CD45+ and NIMP-R14+ cells in vivo. These results indicate that endomucin prevents leukocyte contact with adhesion molecules in non-inflamed tissues and that downregulation of endomucin is critical to facilitate adhesion of leukocytes into inflamed tissues.

Systematical Analysis of the Cancer Genome Atlas Database Reveals EMCN/MUC15 Combination as a Prognostic Signature for Gastric Cancer

“…EMCN, i.e. MUC14, encodes a membrane-bound protein, endothelial sialomucin or mucin-like sialo glycoprotein, which was reported to inhibit cell and extracellular matrix interaction, interfere with leukocyte-endothelial cell adhesion, and even promote the peritoneal metastasis process of GC cells (Liu et al, 2001;Zahr et al, 2016;Dhanisha et al, 2018; FIGURE 3 | Go terms derived from gene set enrichment analysis (GSEA) for top 50 EMCN-and MUC15-correlated genes. The pathways are ranked by -log p-value.…”

Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas

“…It has recently been shown that Bortezomib treatment can suppress MTDH in multiple myeloma (35). EMCN is a membrane protein that could, in theory, be easy to approach if proved to be a major actor in pituitary tumorigenesis (36).…”

“…EMCN did not show involvement in cell migration, nor association with EMT markers. It has recently been shown that EMCN prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions (36). The lack of effect on cell migration by EMCN could be explained by different means, such as: (1) EMCN does not have a role in cell migration of pituitary adenoma cells and our premises were incorrect, (2) technical challenges related to in vitro culturing did not allow us to adequately silence the EMCN gene such as its effect could be recorded, (3) other cells than pituitary adenoma cells (e.g.…”

Leukocyte-endothelial cell interaction is enhanced in podocalyxin-deficient mice

“…In this sense, mice lacking syndecan-1, one of the more abundant components of endothelial glycocalyx, synthesize and maintain a hemodynamically functional glycocalyx layer (Savery et al, 2013). In another study, endomucin, a O-sialoglycoprotein present in the glycocalyx of venules and capillaries, but not of arteries, in adult tissues, has been shown to prevent leukocyte contact with adhesion molecules both under resting and inflammatory conditions (Zahr et al, 2016). Unlike endomucin, Podxl is expressed in major and minor arterial and venous vessels of most tissues.…”