title: Glycol chitosan: A stabilizer of lipid rafts in the intestinal brush border.
abstract: Chitosan is a polycationic polysaccharide consisting of β-(1-4)-linked glucosamine units and due to its mucoadhesive properties, chemical derivatives of chitosan are potential candidates as enhancers for transmucosal drug delivery. Recently, glycol chitosan (GC), a soluble derivative of chitosan, was shown to bind specifically to lipid raft domains in model bilayers. The small intestinal brush border membrane has a unique lipid raft composition with high amounts of glycolipids cross-linked by lectins, and the aim of the present work therefore was to study the interaction of FITC-conjugated GC (FITC-GC) with the small intestinal epithelium. Using organ culture of pig jejunal mucosal explants as a model system, we observed widespread binding of luminal FITC-GC to the brush border. Only little uptake via constitutive endocytosis into apical early endosomes occurred, unless endocytosis was induced by the simultaneous presence of cholera toxin B subunit (CTB). Biochemically, GC bound to microvillus membrane vesicles and caused a change in the density profile of detergent resistant membranes (DRMs). Collectively, the results showed that FITC-GC binds passively to lipid raft domains in the brush border, i.e. without inducing endocytosis like CTB. Instead, and unlike CTB, FITC-GC seems to exert a stabilizing, detergent-protective effect on the lipid raft organization of the brush border.
authors.affiliation: Department of Cellular and Molecular Medicine, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: E Thomas
authors.initials: ET
authors.lastname: Danielsen
authors.affiliation: Department of Cellular and Molecular Medicine, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Denmark. Electronic address: midan@sund.ku.dk.
authors.forename: E Michael
authors.initials: EM
authors.lastname: Danielsen
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008871:Microvilli / Q000737:chemistry* / Q000378:metabolism; D013552:Swine
chemical_list: C118638:glycol-chitosan; D002772:Cholera Toxin; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate
keywords: Brush border; Enterocyte; Glycol chitosan; Lipid raft domains; Small intestine