COMPLEMENT ACTIVATION OF ELECTROGENIC ION-TRANSPORT IN ISOLATED RAT COLON

The complement cascade is an important component in many immune and in flammatory reactions and may contribute to both the diarrhoea and infl ammation associated with inflammatory bowel disease. Isolated rat colo nic mucosae were voltage clamped in Ussing chambers. Basolateral addit ion of zymosan-activated whole human serum (ZAS) induced a rapid onset , transient inward shore circuit current (SCC). This response was conc entration dependent and was significantly attenuated by pre-heating ZA S at 60 degrees C for 30 min. Depletion of complement from normal huma n serum with cobra venom factor (CVF) significantly lowered SCC respon ses. Chloride was the primary charge carrying ion as responses to ZAS were abolished in the presence of the loop diuretic bumetanide. The co mplement component C3a stimulated ion transport but not to the same ex tent as whole serum. Exogenous C5 was without effect. The cyclooxygena se inhibitor piroxicam significantly attenuated the response to ZAS. T hese findings support the possibility that complement activation may c ontribute to the pathophysiology of secretory diarrhoea since activati on of electrogenic chloride secretion converts intestinal epithelia to a state of net fluid secretion. (C) 1997 Elsevier Science Inc.