title: Pathogenic role of mast cells in experimental eosinophilic esophagitis.
abstract: Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal intraepithelial eosinophils, extracellular eosinophil granule deposition, induced mast cell accumulation, and epithelial cell hyperplasia. However, the processes involved in the development of a number of these characteristics are largely unknown. Herein, we tested the hypothesis whether induced mast cell accumulation in the esophagus has a role in promoting EoE pathogenesis. Accordingly, we induced experimental EoE in wild-type mice, mast cell-deficient WWv mice, and mast cell-reconstituted WWv mice. We report that esophageal mast cell numbers increase in parallel with eosinophils in a dose- and time-dependent manner following the induction of allergen-induced EoE. The induced mast cells are localized in the esophageal lamina propria and muscular mucosa but have no influence on promoting esophageal eosinophilia. The 5'-bromodeoxyuridine (BrdU) incorporation analysis indicated that mast cells have a significant role in muscle cell hyperplasia and hypertrophy. In addition, the wild-type and mast cell-reconstituted WWv mice showed a comparable number of BrdU⁺ cells in the esophageal muscular mucosa following allergen-induced EoE. In conclusion, we provide for the first time direct evidence that mast cell promotes muscle cell hyperplasia and hypertrophy and may have a significant role in promoting esophageal functional abnormalities in EoE.
authors.affiliation: Division of Gastroenterology and Liver Disease, Digestive Health Institute, Case Western Reserve University College of Medicine, Cleveland, OH 44106, USA.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Niranjan
authors.forename: Parm
authors.initials: P
authors.lastname: Mavi
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rayapudi
authors.forename: Scott
authors.initials: S
authors.lastname: Dynda
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology; D049108:Cell Enlargement; D004195:Disease Models, Animal; D057765:Eosinophilic Esophagitis / Q000209:etiology / Q000473:pathology*; D004804:Eosinophils / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D009092:Mucous Membrane / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology
chemical_list: D000485:Allergens
keywords: 5′-bromodeoxyuridine; allergen; eosinophilic esophagitis; hyperplasia; hypertrophy; mast cells; muscular mucosa