Galectin-3 promotes sialyl Lewis X epitope biosynthesis in monocytes.

Monocytes play a fundamental role in the inflammatory response to diverse stimuli. A critical early step in the initiation of this response is the recruitment of monocytes from the bloodstream to sites of tissue injury. This migration is tightly regulated at the molecular level through interactions between vascular selectins and sialyl Lewis X (sLeX)-bearing glycoproteins on the surface of monocytes. Galectin-3, a β-galactoside-binding lectin with diverse immunological functions, has been linked to enhanced monocyte recruitment through mechanisms that are still being elucidated. Here, using a combination of genetic and pharmacological inhibition approaches, we show that galectin-3 enhances sLeX epitope biosynthesis in both mouse and human monocytes. This effect is mediated by transcriptional upregulation of α(1,3)-fucosyltransferase 7 (FUT7), a rate-limiting enzyme in sLeX synthesis. Furthermore, we demonstrate that restoring FUT7 activity in galectin-3-deficient monocytes rescues cell surface expression of sLeX. These findings reveal a previously unrecognized role for galectin-3 in regulating monocyte adhesion by directly influencing selectin ligand biosynthesis.