Mediators of anaphylaxis-induced ion transport changes in small intestine

Abstract

Net ion transport by jejunum of rats immunized against Trichinella spiralis on challenge with parasite-derived antigen was measured in Ussing chambers as a rapidly expressed, biphasic rise and fall (phase I and II) in short-circuit current (delta Isc). This delta Isc is triggered by mucosal anaphylaxis. Our objective is to identify mast cell-derived substances that mediate the epithelial response. Antigenic challenge of sensitized jejunum caused the release of 5-hydroxytryptamine (5-HT), histamine, and prostaglandin E2 (PGE2). The antigen-induced phase I response was mimicked by exogenous 5-HT or histamine and blocked by pretreatment of tissue with 5-HT and histamine H1-antagonists; the phase II response was mimicked by exogenous PGE2 and blocked by an inhibitor of prostaglandin synthesis. Atropine and tetrodotoxin significantly blunted the phase I response as well as the delta Isc caused by exogenous 5-HT or histamine while only slightly reducing the phase II response and not affecting the delta Isc induced by PGE2. Results support the conclusion that 5-HT, histamine, and PGE2 mediate the antigen-induced change in Isc through direct and neurally mediated stimulation of jejunal epithelium.

Role of mast cells in ion transport abnormalities associated with intestinal anaphylaxis. Correction of the diminished secretory response in genetically mast cell-deficient W/Wv mice by bone marrow transplantation.

“…The mediators then act on target cells to cause alterations in physiology. In rat intestine, evidence has been provided for the involvement of histamine, serotonin, and prostaglandins in antigen-induced transport changes (13,14). The changes are thought to occur by the effects of mast cell mediators acting directly on the epithelium and/or indirectly via stimulated intestinal nerves (13)(14)(15).…”

“…The potential importance of mast cell mediator release in the production of intestinal transport abnormalities is supported by pharmacological studies with drugs that influence either mast cell activation or the end organ effects of mast cell-associated mediators (9,(11)(12)(13)(14). Recent morphological, pharmacological, and electrophysiological evidence indicates that interactions between enteric nerves and mast cells may importantly participate in some ofthese responses (1 1, 13-16).…”

Antigen Absorption by the Jejunal Epithelium of Children with Cow's Milk Allergy

“…The increase in Isc in the active phase of the disease is reminiscent of the increase in Isc due to active chloride secretion after luminal ovalbumin challenge in rats already sensitized to ovalbumin (25). There is considerable evidence that the antigen stimulation of plasmocytes in the lamina propria of the gut mucosa produces an increase in Isc due to the liberation of many mediators that directly or undirectly stimulate water and electrolyte secretion (26). In our experiments, the increase in Isc could be due to the persistence of chloride secretion induced by cow's milk proteins in vivo.…”

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

“…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.…”