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Ontogenic and functional analysis of intestinal galectin-3

Abstract:

Galectins are a family of animal lectins with affinity for β-galactose and N-acetyl glucosamine residues. While studying, via immunocytochemistry, macrophage subsets in the intestinal lamina propria of mice we encountered the unexpected observation that galectin-3, an activated macrophage marker, was also expressed by colonic but not by small intestinal (SI) epithelial cells. Herein, we report results from subsequent studies designed to fully characterize ontogenic, regional and spatial patterns of intestinal galectin-3 expression. Immunohistological studies with an anti-galectin-3 mAb (M3/38) revealed that SI galectin-3 expression was developmentally regulated being low prior to weaning, transiently and markedly increased around weaning, and very low or absent by the fourth postnatal week. In contrast, galectin-3 was abundantly expressed by colonic epithelial cells independent of age in both pre- and post-weaning mice. Further, large intestinal galectin-3 was restricted to epithelial cuff regions and absent in crypt epithelium. Binding assays of enterobacterial lipopolysaccharide (LPS) with cell surface galectin-3 demonstrated that LPS containing intact lipid A and the core oligosaccharide region such as Escherichia coli 011:B4 LPS specifically bound galectin-3 on colonic epithelial cells but not mutant LPS derived from Salmonella Minnesota Re and lacking carbohydrate residues in the core region. The striking ontogenic, regional and spatial patterns of intestinal galectin-3 expression, considered together with its carbohydrate binding specificities and ability to bind LPS, support the working hypothesis that colonic galectin-3 may contribute to innate immunity in this bacterial dense compartment.