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Eosinophils alter colonic epithelial barrier function: role for major basic protein.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2005 Nov; Vol. 289 (5), pp. G890-7. - Publication Year :
- 2005
-
Abstract
- Mucosal eosinophils increase in a number of gastrointestinal diseases that are often associated with altered epithelial barrier function, including food allergic enteropathies and inflammatory bowel diseases. Although eosinophils are known to secrete biologically active mediators including granule proteins, their role in gastrointestinal diseases is uncertain. The aim of this study was to determine the impact of eosinophils on intestinal barrier function. Epithelial barrier function was determined in a coculture of eosinophils and T84 epithelial cells and in a murine model of T helper (Th) type 2-mediated colitis. Coculture conditions resulted in decreased transepithelial resistance (TER) and increased transepithelial flux. Cell-free coculture supernatants contained a > or =5-kDa soluble factor that also diminished TER; these supernatants contained the eosinophil-granule proteins major basic protein (MBP) and eosinophil-derived neurotoxin (EDN). T84 barrier function decreased significantly when basolateral surfaces were exposed to native human MBP but not EDN. Additional studies identified downregulation of the tight junctional molecule occludin as at least one mechanism for MBP action. MBP-null mice were protected from inflammation associated with oxazolone colitis compared with wild-type mice. In conclusion, MBP decreases epithelial barrier function and in this manner contributes to the pathogenesis of inflammatory bowel diseases.
- Subjects :
- Animals
Cells, Cultured
Colitis chemically induced
Colon cytology
Epithelial Cells
Gene Expression Regulation
Humans
Intestinal Mucosa cytology
Mice
Mice, Knockout
RNA, Messenger genetics
RNA, Messenger metabolism
Colon physiology
Eosinophil Major Basic Protein physiology
Eosinophils physiology
Epithelium physiology
Intestinal Mucosa physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1857
- Volume :
- 289
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16227527
- Full Text :
- https://doi.org/10.1152/ajpgi.00015.2005