Fucosylation Of Endomucin By FucT-Ⅶ May Contribute To Up-regulating Monocyte Adhesion To Vascular Endothelial Cell Induced By IL-1B

Vascular endothelium is continuous coverage in systemic vascularintima cell populations, studies have found endothelial layer is not onlyblood and tissue barrier, but also possesses a variety of other functions. Inview of the physiological function of vascular endothelial cells, vascularendothelial cells injury become actuating link of many diseases such asatherosclerosis, hypertension, diabetes and so on. Atherosclerosis is avascular endothelial injury caused by inflammatory response characterizedby lesions of chronic diseases of the vascular wall. The adhesion ofendothelial cells and monocytes in the inflammatory response in thisprocess involves the monocyte many adhesion molecules of the endothelialcells. Previous studies have shown that the adhesion process with the cellsurface of endothelial cells and mononuclear cells related to the amount ofthe expression of adhesion molecules, and may be related to the expressionof the chemokine. Therefore, the discussion on the function of theendothelial cell membrane protein glycosylation mechanism revealsendothelium-monocyte interaction plays a vital role in the procession of atherosclerosis.The carbohydrate sialyl Lewis X (sLex) is fucosylatedglycoconjugates involved in the development of several pathologies. Theadhesion of sialyl Lewis X to selectins is a key step during inflammatoryprocesses. Synthesis of sLex depends on activity of fucosyltransferaseswhich add fucose to precursor glycan structures, includingα-1,3-fucosyltransferase(FucT-Ⅶ). The glycosidic component ofendomucin plays a key role in the adhesion between endothelial cells andmonocytes. Here, we observed that the adhesion potential of monocytes toendothelial cells was enhanced by IL-1β. Meanwhile the level of FucT-Ⅶand sLex in EA.hy926cells was increased by IL-1β. Deletion of FucT-Ⅶgene by siRNAs in EA.hy926cells suspends the adhesion potential ofmonocytes to EA.hy926cells induced by IL-1β. The enhanced adhesionwere also significantly inhibited by functional blockade with antibodiesagainst endomucin or sLex in FucT-Ⅶ transfected cells.It wasdemonstrated that endomucin and sLex acted as an essential interfacebetween heterogeneous cells. Moreover, the sLex modification onendomucin was enhanced in EA.hy926cells, when it was not onlystimulated by IL-1β, but also transfected with FucT-Ⅶ plasmid.Furthermore, P38or ERK inhibitors pre-treatment down-regulated thehighly elevated expression of FucT-Ⅶ and the adhesion of THP-1cells toendothelial cells induced by IL-1β. Taken together, our results suggest that increased FucT-Ⅶ activity due to inflammatory cytokine induction inhuman endothelial cells resulted in enhancement of endomucin-dependentvascular endothelium-monocytes adhesion which correlated with MAPKpathway including p38and ERK.This indicated that FucT-Ⅶ can be targetsfor the development of new strategies to against inflammation-dependentconditions.