DISRUPTION OF INTESTINAL BARRIER FUNCTION-ASSOCIATED WITH EXPERIMENTAL COLITIS - POSSIBLE ROLE OF MAST-CELLS

The objective was to characterize changes in barrier and transport fun ction in an experimental model of colitis, and to determine whether ma st cells contribute to these changes. Colitis was induced in rats with intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS, 30 mg) in 50% ethanol. Controls received 0.9% saline or the ethanol vehicle alone. I n vivo loop perfusion was used to assess colonic water flux (in mu l.c m(-1).h(-1)) and lumen-to-blood Cr-51-labeled EDTA clearance (% admini stered dose) after TNBS. Myeloperoxidase (MPO) was used as an index of granulocyte influx. TNBS or its vehicle caused a marked decrease in w ater absorption and an increase in permeability at 4 h after administr ation compared with saline. Neither dexamethasone (anti-inflammatory c ontrol) nor doxantrazole (mast cell stabilizer) was able to attenuate these early changes likely caused by the vehicle. In contrast, at late r times, TNBS (but not its vehicle) also increased Cr-51-EDTA permeabi lity and decreased water absorption; both effects were significantly a ttenuated by dexamethasone or doxantrazole. These drugs also significa ntly reduced TNBS-induced MPO accumulation and release of rat mast cel l protease II. We conclude that experimental colitis is associated wit h severe defects in intestinal transport and barrier functions and tha t mast cells may contribute to the pathogenesis of these changes.