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Acute inflammation alters bicarbonate transport in mouse ileum
Author(s) -
Zhang Hui,
Ameen Nadia,
Melvin James E.,
Vidyasagar Sadasivan
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.129262
Subject(s) - ileum , ussing chamber , cystic fibrosis transmembrane conductance regulator , medicine , chemistry , endocrinology , secretion , inflammation , cystic fibrosis , bicarbonate , ileitis , western blot , biology , crohn's disease , biochemistry , disease , gene
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 HCO 3 − ‐rich plasma‐like fluid. However, the regulation and mechanisms of HCO 3 − 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 ( I sc ) (0.58 ± 0.07 μEq h −1 cm 2 versus 1.63 ± 0.14 μEq h −1 cm 2 ). The cAMP‐stimulated I sc 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 HCO 3 − secretion, measured using a pH stat technique, was decreased significantly in anti‐CD3‐injected mice, with a simultaneous increase in Cl − ‐independent HCO 3 − secretion that was also inhibited by glibenclamide. Experiments using Cftr −/− mice showed neither an increase in I sc nor an increase in HCO 3 − 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 − HCO 3 − exchange in normal mice, to a predominantly electrogenic anion secretion including HCO 3 − that occurs via functional Cftr during anti‐CD3‐mediated acute inflammation.