MAST-CELL MEDIATED ION-TRANSPORT IN INTESTINE FROM PATIENTS WITH AND WITHOUT INFLAMMATORY BOWEL-DISEASE

Background-Mast cells have been shown to regulate intestinal ion trans port in animal models and normal human colon but their physiological r ole in human intestinal inflammatory disorders is unknown. Aims T-exam ine mast cell regulation of ion transport in inflammatory bowel diseas e (IBD). Subjects and methods-Small and large intestine was obtained f rom patients with and without IBD undergoing surgical resection. Short circuit current (Isc) responses to rabbit antihuman IgE, histamine, a nd electrical stimulation were measured in Ussing chambers. Specimens were also examined for mast cell numbers and degree of inflammation. R esults-Isc responses to anti-IgE and histamine were smaller in magnitu de in IBD compared with non-IBD tissues. In all tissues, anti-IgE Ise responses were reduced by about 80% in chloride free buffer. The hista mine H-1 receptor antagonist, pyrilamine, decreased anti-IgE responses in non-IBD tissues. Greater inhibition with pyrilamine was seen in IB D small intestine but its effect was less in IBD colon. Histamine pret reatment of non-IBD control tissues reduced anti-IgE responses to leve ls seen in IBD colon but had no effect in small intestine. Mast cell n umbers were greater in IBD compared with non-IBD small intestine while no differences were observed between the colonic groups. Isc response s to anti-IgE were not correlated with the degree of mucosal inflammat ion. Conclusions-This study provides further evidence that mast cells are capable of mediating alterations of ion transport in human gut but that this regulatory role may be altered in IBD. The data suggest tha t prior activation of mast cells with release of histamine may account for the reduced secretory response to anti-IgE observed in IBD coloni c tissues.