Galectin-3 Promotes Sialyl LewisX Biosynthesis in Monocytes 4781

Abstract Description Purpose Galectin-3 initiates monocyte migration; however, the precise mechanism of promoting trafficking remains unclear. Monocyte extravasation involves adhesive interactions between vascular selectins and sialyl LewisX (sLeX) bearing glycans on the surface of circulating monocytes. Our study aimed to investigate whether galectin-3 influences monocyte sLeX expression and adhesive capacities. Methods Galectin-3 knockout (Gal3−/−) and wild-type (WT) were isolated from the blood. Human monocytes were extracted from blood and Galectin-3 expression was inhibited using galectin-3 siRNA (siGal3) and the thiodigalactoside analog TD139. Parallel plate flow chamber assays assessed the adhesion of galectin-3-deficient monocytes. Results Inhibiting galectin-3 in activated human and murine monocytes reduced sLeX expression, whereas adding recombinant galectin-3 increased sLeX levels. This deficiency correlated with impaired recruitment of Gal3−/− monocytes into wounded corneas of WT chimeric mice. PCR array analysis revealed that galectin-3 promotes sLeX biosynthesis by upregulating FUT7 expression. Enforced fucosylation of galectin-3-deficient monocytes restored their rolling capacity on activated endothelial cells under flow in vitro. Conclusions These findings identify a novel mechanism where galectin-3 enhances monocyte recruitment by upregulating FUT7 expression thereby enhancing sLeXbiosynthesis. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)