Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease

Abstract

Background-Mast cells have been shown to regulate intestinal ion transport in animal models and normal human colon but their physiological role in human intestinal inflammatory disorders is unknown. Aims-To examine mast cell regulation of ion transport in inflammatory bowel disease (IBD). Subjects and methods-Small and large intestine was obtained from patients with and without IBD undergoing surgical resection. Short circuit current (Isc) responses to rabbit antihuman IgE, histamine, and electrical stimulation were measured in Ussing chambers. Specimens were also examined for mast cell numbers and degree of inflammation. Results-Isc responses to anti-IgE and histamine were smaller in magnitude in IBD compared with non-IBD tissues. In all tissues, anti-IgE Isc responses were reduced by about 80% in chloride free buVer. The histamine H 1 receptor antagonist, pyrilamine, decreased anti-IgE responses in non-IBD tissues. Greater inhibition with pyrilamine was seen in IBD small intestine but its eVect was less in IBD colon. Histamine pretreatment of non-IBD control tissues reduced anti-IgE responses to levels seen in IBD colon but had no eVect in small intestine. Mast cell numbers were greater in IBD compared with non-IBD small intestine while no differences were observed between the colonic groups. Isc responses to anti-IgE were not correlated with the degree of mucosal inflammation. 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 that prior activation of mast cells with release of histamine may account for the reduced secretory response to anti-IgE observed in IBD colonic tissues. (Gut 1997; 41: 785-792)

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

“…Similar diminished Isc responsiveness has been observed in other animal models of colitis and in tissue resections from patients with inflammatory bowel disease. [31][32][33][34] However, neither ROL nor PTX treatment led to any amelioration of the reduced Isc responses, clearly indicating uncoupling of structure and function in this model of colitis. Juxtaposition of these data with the histological portion of the study suggests that either regulation of Isc is more readily altered than derangement of colon structure, or that ion transport and colon structure are regulated by different mechanisms.…”

Mast Cells and Irritable Bowel Syndrome: From the Bench to the Bedside

“…In sensitized mast cell-deficient mice, secretory response to serosal antigen was reduced by 70% in comparison to normal congenic mice, but fully restored after reconstitution of intestinal mast cell population by injecting bone marrow-derived mast cell precursors. 11,59 Others demonstrated that the compound 48/80-induced and anti-IgE-induced secretory response could be reduced by ketotifen and H 1 R antagonist in chicken ileum 60 and human colon, 57 respectively. Furthermore, SP stimulated net ion secretion could be reduced partly by H 1 R and H 2 R antagonists and a mast cell stabilizer (doxantrazole).…”

“…55,56 In vitro studies have clearly demonstrated that MC activation alters intestinal epithelial ion transport directly or indirectly (via intrinsic or extrinsic nerves), 57,58 through recording the transepithelial short-circuit current of the intestinal mucosal tissues or epithelial cell monolayers. In sensitized mast cell-deficient mice, secretory response to serosal antigen was reduced by 70% in comparison to normal congenic mice, but fully restored after reconstitution of intestinal mast cell population by injecting bone marrow-derived mast cell precursors.…”

Tissue Eosinophilia in a Mouse Model of Colitis Is Highly Dependent on TLR2 and Independent of Mast Cells

“…Mast cells have been shown by a number of groups to modify the epithelial barrier function within the intestine and, when activated, to increase intestinal permeability and fluid loss. [53][54][55][56][57] Such processes could explain enhanced weight loss in mast cell-containing animals.…”