Mucosal Pathophysiology and Inflammatory Changes in the Late Phase of the Intestinal Allergic Reaction in the Rat

摘要

Relatively little information exists concerning the late phase of the allergic reaction in the gastrointestinal tract. Here, we characterized jejunal mucosal pathophysiology and inflammation after oral antigen challenge of sensitized rats, and examined the role of mast cells in events after challenge. Sprague-Dawley rats, mast cell-deficient (Ws/Ws), and +/+ control rats were sensitized to horseradish peroxidase, and challenged intragastrically with antigen 14 days later. Jejunal segments were obtained at 0.5 to 72 hours after challenge for functional assessment in Ussing chambers and for morphological assessment by light and electron microscopy. Intestine from sensitized Sprague-Dawley rats demonstrated enhanced ion secretion and permeability at all times after challenge. Electron microscopy revealed abnormal mitochondria within enterocytes and disruption of the epithelial basement membrane associated with influx into the mucosa of mast cells, eosinophils, neutrophils, and mononuclear cells. Many inflammatory cells appeared activated. In contrast, antigen-challenged Ws/Ws rats demonstrated no functional changes or inflammatory cell infiltrate. We conclude that oral antigen challenge of sensitized rats induces sustained epithelial dysfunction. Mast cells mediate both epithelial pathophysiology and recruitment of additional inflammatory cells that may contribute to persistent pathophysiology and symptoms.