Histamine release from gut mast cells from patients with inflammatory bowel diseases.

Abstract

Inflammatory mediators from intestinal mast cells may serve as initiators of acute and delayed inflammation. Mast cell histamine release was measured in 19 patients with inflammatory bowel diseases using gut mast cells from enzymatically dispersed endoscopic forceps biopsy specimens of macroscopically inflamed and normal tissue. Mast cells and corresponding basophils were challenged with anti-IgE, anti-IgG, subclass anti-IgG4, and formyl-methionyl-leucyl-phenylalanine (FMLP) and results were compared with those from nine patient control subjects.The mast cell count in patients with ulcerative colitis was increased compared with that in control subjects and patients with Crohn's disease, and the mast cell count obtained from inflamed tissue was greater than that of normal tissue. The study also shows the heterogeneity of the responsiveness of the histamine releasing cells to various secretagogues. Thus, mast cells released 0 4 (0.0-2.0) (median (range)) ng histamine per sample at anti-IgE challenge, and basophils were also anti-IgE responsive. In contrast, mast cells did not respond to FMLP but the corresponding basophils did. Gut mast cells released 0*3 (0.0-1-0) (median (range)) ng histamine per sample at anti-IgG4 challenge; however, the corresponding basophils did not respond to anti-IgG4. In addition, the anti-IgG4 mediated histamine release was primarily confined to patients with inflammatory bowel disease.This study substantiates previous histopathological findings that mast cells may play a functional role in the inflammatory process of inflammatory bowel diseases and provides evidence for a possible role of subclass IgG4 as a reaginic antibody.

Short exposure of intestinal epithelial cells to TNF-α and histamine induces Mac-1-mediated neutrophil adhesion independent of protein synthesis

“…Histamine is stored in mast cells and extracellularly released by stimulation [14]. It has been demonstrated that concentrations of TNF-␣, histamine, and IL-8 are increased in the affected intestinal mucosa of inflammatory bowel diseases [16][17][18][19][20]39], and symptoms correlate with the magnitude of neutrophil accumulation in the intestinal epithelium and mucosa [7]. In this study, we have revealed that stimulation of intestinal epithelial cells with TNF-␣ or hista-mine increases neutrophil adhesion to epithelial cells, and that stimulation of neutrophils with IL-8 or TNF-␣ up-regulates surface expression of CD11b/CD18 molecules and increases neutrophil adhesion to epithelial cells.…”

“…Histamine content and its secretion have been found to be significantly increased particularly in affected mucosa of ulcerative colitis and Crohns disease compared with unaffected tissues [16,17]. Moreover, TNF-␣ concentrations are demonstrated to be markedly increased in the affected intestinal mucosa, serum, and feces of active inflammatory bowel diseases [18][19][20].…”

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

“…Mast cells in the lamina propria and submucosa have been implicated as contributors to local inflammation during IBD because of their ability to synthesize mediators such as histamine, prostaglandins, leukotrienes, cytokines, chemokines, and proteases. 15,35,36 The W sh mice were found to be more resistant to DSS-induced weight loss and mucosal damage in the cecum than C57BL/6 mice, a process that was confirmed to be mast cell-dependent by reconstitution studies. 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.…”

“…15,35,36 To date, no reported studies have examined the contribution of the mast cell during DSS colitis using mast cell-deficient Kit W-sh/W-sh (W sh ) mice. Mast cell-deficient mice, wild-type C57BL/6, and W sh mice reconstituted intravenously with 7.5 ϫ 10 6 C57BL/6 BMMCs were all treated with 3% DSS for 5 days, followed by 2 or 5 days of regular drinking water.…”

“…29 -34 Mast cells have been suggested to play a proinflammatory role in models of colitis, and there is some evidence of mast cell activation in human IBD. 15,35,36 Mast cells are considered an important source of cytokines, chemokines, and other signaling factors that initiate the recruitment of eosinophils into sites of allergic inflammation. [37][38][39] Specifically, in the gastrointestinal tract mucosal mast cells can produce significant amounts of IL-5, CCL11, and LTC 4 after IgE-mediated stimulation, making them key cells to study in disease processes associated with eosinophilia.…”