title: Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract.
abstract: Purified human mucins from different parts of the intestinal tract (ileum, cecum, transverse and sigmoid colon and rectum) were isolated from two individuals with blood group ALe(b) (A-Lewis(b)). After alkaline borohydride treatment the released oligosaccharides were structurally characterized by nano-ESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem MS) without prior fractionation or derivatization. More than 100 different oligosaccharides, with up to ten monosaccharide residues, were identified using this technique. Oligosaccharides based on core 3 structures, GlcNAc(beta1-3)GalNAc (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetylgalactosamine), were widely distributed in human intestinal mucins. Core 5 structures, GalNAc(alpha1-3)GalNAc, were also recovered in all fractions. Moreover, a comparison of the oligosaccharide repertoire, with respect to size, diversity and expression of glycans and terminal epitopes, showed a high level of mucin-specific glycosylation: highly fucosylated glycans, found specifically in the small intestine, were mainly based on core 4 structures, GlcNAc-(beta1-3)[GlcNAc(beta1-6)]GalNAc, whereas the sulpho-Le(X) determinant carrying core 2 glycans, Gal(beta1-3)[GlcNAc(beta1-6)]-GalNAc (where Gal is galactose), was recovered mainly in the distal colon. Blood group H and A antigenic determinants were present exclusively in the ileum and cecum, whereas blood group Sd(a)/Cad related epitopes, GalNAc(beta1-4)[NeuAc(alpha2-3)]Gal (where NeuAc is N-acetylneuraminate), were found to increase along the length of the colon. Our findings suggest that mucins create an enormous repertoire of potential binding sites for micro-organisms that could explain the regio-specific colonization of bacteria in the human intestinal tract.
authors.affiliation: Unité Mixte de Recherche CNRS/USTL 8576, Glycobiologie Structurale et Fonctionnelle, IFR 118, Université des Sciences et Technologies de Lille 1, 59655 Villeneuve d'Ascq Cedex, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Robbe
authors.forename: Calliope
authors.initials: C
authors.lastname: Capon
authors.forename: Bernadette
authors.initials: B
authors.lastname: Coddeville
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
mesh_terms: D002102:Cadaver; D002240:Carbohydrate Sequence; D005591:Chemical Fractionation / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003106:Colon / Q000737:chemistry; D005643:Fucose / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000737:chemistry*; D016030:Kidney Transplantation; D007983:Lewis Blood Group Antigens / Q000737:chemistry; D008297:Male; D009077:Mucins / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D009438:Neuraminic Acids / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013463:Sulfuric Acid Esters / Q000378:metabolism; D014019:Tissue Donors
chemical_list: D007983:Lewis Blood Group Antigens; D009077:Mucins; D009438:Neuraminic Acids; D011134:Polysaccharides; D013463:Sulfuric Acid Esters; D005643:Fucose