Acute inflammation alters bicarbonate transport in mouse ileum

摘要: T-cell mediated acute inflammation of the ileum may occur during Crohn's disease exacerbations. During ileal inflammation, absorption nutrients and electrolytes by villus cells is decreased with a concomitant increase in crypt and/or fluid secretion. These alterations lead to accumulation subsequent diarrhoea. Net intestinal secretion consists HCO3−-rich plasma-like fluid. However, regulation mechanisms HCO3− normal acutely inflamed are not clearly understood. To study this phenomenon, anti-CD3 monoclonal antibody (mAb)- induced vivo inflammatory mouse models was used for vitro functional studies Ussing chamber pH stat techniques. Three hours after mAb injection, mucosa stripped muscular serosal layers showed significant short circuit current (Isc) (0.58 ± 0.07 μEq h−1 cm2versus 1.63 0.14 cm2). The cAMP-stimulated Isc component sensitive glibenclamide but DIDS, suggesting that cystic fibrosis transmembrane conductance regulator (Cftr)-mediated anion responsible. Basal Cl−-dependent secretion, measured using technique, significantly anti-CD3-injected mice, simultaneous Cl−-independent also inhibited glibenclamide. Experiments Cftr−/− mice neither an nor confirming role Cftr protein stimulating following treatment. Western blot analysis indicated levels were unaltered treatment, at least acutely. Finally, immunoassay cAMP increases intracellular cells, cells. therefore suggest shift from predominantly electroneutral Cl−HCO3− exchange electrogenic including occurs via anti-CD3-mediated inflammation.