title: Acute inflammation alters bicarbonate transport in mouse ileum.
abstract: T-cell mediated acute inflammation of the ileum may occur during Crohn's disease exacerbations. During ileal inflammation, absorption of nutrients and electrolytes by villus cells is decreased with a concomitant increase in crypt and/or villus fluid secretion. These alterations lead to fluid accumulation and the subsequent diarrhoea. Net intestinal fluid secretion consists of HCO3--rich plasma-like fluid. However, the regulation and mechanisms of HCO3- secretion in normal and acutely inflamed ileum are not clearly understood. To study this phenomenon, anti-CD3 monoclonal antibody (mAb)- induced in vivo ileal inflammatory mouse models was used for in vitro functional studies with Ussing chamber and pH stat techniques. Three hours after anti-CD3 mAb injection, ileal mucosa stripped of muscular and serosal layers showed a significant increase in short circuit current (Isc) (0.58+/-0.07 microEq h(-1) cm2 versus 1.63+/-0.14 microEq h(-1) cm2). The cAMP-stimulated Isc component was sensitive to glibenclamide but not to DIDS, suggesting that a cystic fibrosis transmembrane conductance regulator (Cftr)-mediated anion conductance was responsible. Basal Cl--dependent HCO3- secretion, measured using a pH stat technique, was decreased significantly in anti-CD3-injected mice, with a simultaneous increase in Cl--independent HCO3- secretion that was also inhibited by glibenclamide. Experiments using Cftr-/- mice showed neither an increase in Isc nor an increase in HCO3- secretion, confirming the role for Cftr protein in stimulating anion secretion following anti-CD3 treatment. Western blot analysis indicated that Cftr protein levels were unaltered by anti-CD3 treatment, at least acutely. Finally, an immunoassay for cAMP showed significant increases in intracellular cAMP in villus cells, but not in crypt cells. These studies therefore suggest a shift from a predominantly electroneutral Cl-HCO3- exchange in normal mice, to a predominantly electrogenic anion secretion including HCO3- that occurs via functional Cftr during anti-CD3-mediated acute inflammation.
authors: Digestive Diseases, Department of Medicine, Center for Oral Biology, University of Rochester School of Medicine, 601 Elmwood Ave, Box 646, Rochester, NY 14642, USA.
authors: Hui
authors: H
authors: Zhang
authors: Nadia
authors: N
authors: Ameen
authors: James E
authors: JE
authors: Melvin
authors: Sadasivan
authors: S
authors: Vidyasagar
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000208:Acute Disease; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D001639:Bicarbonates / Q000378:metabolism*; D017252:CD3 Complex / Q000276:immunology; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D003967:Diarrhea / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D007419:Intestinal Secretions / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009579:Nitrobenzoates / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D001639:Bicarbonates; D017252:CD3 Complex; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D020536:Enzyme Activators; D009579:Nitrobenzoates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D005905:Glyburide