Dynamic changes in cell-surface expression of mannose in the oral epithelium during the development of graft-versus-host disease of the oral mucosa in rats

Hironori Hanada,Jun Ohno,Kei Seno,Nobutaka Ota,Koki Taniguchi

doi:10.1186/1472-6831-14-5

Abstract

BackgroundThe role of cell-surface glycoconjugates in oral mucosal graft-versus-host disease (GVHD) is still unclear, even though molecular changes in the oral epithelium are essential for the pathogenesis of these lesions. In this study, we investigated changes in the binding of mannose (Man)-specific Lens culinaris lectin (LCA) in the oral mucosa of rats with GVHD.MethodsLewis rat spleen cells were injected into (Lewis x Brown Norway) F1 rats to induce systemic GVHD, including oral mucosal lesions. Tongue and spleen samples were evaluated using lectin histochemistry, immunohistochemistry, Western blotting, transwell migration assays and Stamper-Woodruff binding assays.ResultsBinding of Man-specific LCA expanded to the epithelial layers of the tongue in GVHD-rats. An expansion of LCA binding was related to the increased expression of mannosyltransferase in the oral mucosa. CD8+ cells, effector cells of oral mucosal GVHD, expressed mannose-binding protein (MBP) and migrated to the medium containing Man in the transwell migration assay. Adherence of CD8+ cells to the oral epithelium could be inhibited by pretreating CD8+ cells with MBP antibody and/or by pretreating sections with Man-specific LCA.ConclusionsIncreased expression of Man on keratinocytes leads to the migration and/or adhesion of CD8+ cells in the surface epithelium, which is mediated in part by the MBP/Man-binding pathway during the development of oral mucosal GVHD.

Highlights

The role of cell-surface glycoconjugates in oral mucosal graft-versus-host disease (GVHD) is still unclear, even though molecular changes in the oral epithelium are essential for the pathogenesis of these lesions
The results indicate that during the development of oral mucosal GVHD in rats, increased expression of Man by KCs leads to the migration and/or adhesion of CD8+ cells in the surface epithelium, mediated in part by the mannose-binding protein (MBP)/ Man-binding pathway
Oral mucosal GVHD is characterized by intercellular adhesion molecule-1 (ICAM-1) expression and CD8+ T-cell infiltrates First we examined whether immunohistochemical characteristics could be detected in the oral mucosa during the development of GVHD

Summary

Introduction

The role of cell-surface glycoconjugates in oral mucosal graft-versus-host disease (GVHD) is still unclear, even though molecular changes in the oral epithelium are essential for the pathogenesis of these lesions. Lectin binding is modified during the process of epithelial differentiation and injury stimulation of the skin and oral mucosa [10,11,12,13] Among those lectins, Lens culinaris lectin (LCA), known as a mannose (Man) binder, possesses unique binding specificities, with a biantennary core of 1,6-fucosylated oligosaccharides and glycans of human serum transferrin and αfetoprotein [14]. Cell surface Man is a ligand for mannose-binding protein (MBP), which functions in opsonization of microorganisms for phagocytes and cellmediated cytotoxicity-antitumor activity [14,15] These studies have led to the hypothesis that determining changes in Man expression on KCs will aid in understanding the pathogenesis of oral mucosal GVHD. The results indicate that during the development of oral mucosal GVHD in rats, increased expression of Man by KCs leads to the migration and/or adhesion of CD8+ cells in the surface epithelium, mediated in part by the MBP/ Man-binding pathway

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Discussion

Conclusion