title: Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease.
abstract: The intestinal permeability of undegraded α9-gliadin peptide 31-49 (p31-49) and 33-mer gliadin peptides is increased in active celiac disease. Two distinct transport pathways have been proposed: paracellular leakage through epithelial tight junctions and protected transcellular transport. To analyze the relative contribution of these pathways, we compared mucosa-to-serosa permeability of small and large permeability markers [ionic conductance (G), mannitol, 182 Da; horseradish peroxidase, 40 kDa] and gliadin peptides [33-mer (p56-88, 3900 Da), 19-mer (p31-49, 2245 Da; and p202-220, 2127 Da), and 12-mer (p57-68, 1453 Da)] in duodenal biopsy specimens mounted in Ussing chambers. The permeability of intact peptides was much higher for p31-49 or 33-mer than for horseradish peroxidase, p202-220, and p57-68. A positive correlation was observed between G, an index of paracellular diffusion of ions, and mannitol permeability. The absence of correlation between G and permeability to intact 33-mer or p31-49 did not favor paracellular diffusion of the peptides. Immunofluorescence studies indicated that 33-mer enters the early endosome antigen 1-positive compartment but escapes the lysosomal-associated protein 2-positive compartment. The results underline that mannitol and ionic conductance G cannot be considered markers of permeability to gliadin peptides. In active celiac disease, increases in transcellular permeability to intact gliadin peptides might be considered in treatment strategies aimed at controlling epithelial permeability to gluten.
authors: INSERM, Unit 989, Paris, France; The University of Paris, Descartes, Paris, France.
authors: Sandrine
authors: S
authors: Ménard
authors: Corinne
authors: C
authors: Lebreton
authors: Michael
authors: M
authors: Schumann
authors: Tamara
authors: T
authors: Matysiak-Budnik
authors: Christophe
authors: C
authors: Dugave
authors: Yoram
authors: Y
authors: Bouhnik
authors: Georgia
authors: G
authors: Malamut
authors: Christophe
authors: C
authors: Cellier
authors: Matthieu
authors: M
authors: Allez
authors: Pascal
authors: P
authors: Crenn
authors: Joerg Dieter
authors: JD
authors: Schulzke
authors: Nadine
authors: N
authors: Cerf-Bensussan
authors: Martine
authors: M
authors: Heyman
mesh_terms: D001692:Biological Transport; D002446:Celiac Disease / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D005903:Gliadin / Q000493:pharmacokinetics*; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008353:Mannitol / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D010539:Permeability; D012704:Serous Membrane / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D008353:Mannitol; D005903:Gliadin; D006735:Horseradish Peroxidase