BACKGROUND: Proteoglycans, consisting of glycosaminoglycan (GAG) side chains covalently linked to a protein core, are a major component of the extracellular matrix of the intestinal lamina propria. AIMS: This study investigated the effects of lamina propria T cell activation on the proteoglycan component of the matrix. METHODS: The high degree of sulphation of GAGs means that they are polyanionic and thus can be visualised in tissue sections by means of colloidal-gold labelled cationic probes. RESULTS: In human fetal small intestine there is a dense meshwork of anionic residues in the lamina propria and basement membrane. When explants of human fetal small intestine are cultured ex vivo, and resident lamina propria T cells are activated with pokeweed mitogen, mucosal destruction occurs within three days. This is associated with the rapid loss of anionic sites from the lamina propria. Dermatan sulphate proteoglycan is lost from the tissue and is present at increased concentrations in the organ culture supernatants, indicating that T cell activation has led to solubilisation of lamina propria proteoglycans. Tissue destruction and loss of anionic residues are inhibited in a dose dependent fashion by dexamethasone, and by the protease inhibitor, alpha 2 macroglobulin. CONCLUSIONS: Proteolytic degradation of the lamina propria may therefore be a mechanism by which T cell hypersensitivity injures the intestinal mucosa.
BACKGROUND: Proteoglycans, consisting of glycosaminoglycan (GAG) side chains covalently linked to a protein core, are a major component of the extracellular matrix of the intestinal lamina propria. AIMS: This study investigated the effects of lamina propria T cell activation on the proteoglycan component of the matrix. METHODS: The high degree of sulphation of GAGs means that they are polyanionic and thus can be visualised in tissue sections by means of colloidal-gold labelled cationic probes. RESULTS: In human fetal small intestine there is a dense meshwork of anionic residues in the lamina propria and basement membrane. When explants of human fetal small intestine are cultured ex vivo, and resident lamina propria T cells are activated with pokeweed mitogen, mucosal destruction occurs within three days. This is associated with the rapid loss of anionic sites from the lamina propria. Dermatan sulphate proteoglycan is lost from the tissue and is present at increased concentrations in the organ culture supernatants, indicating that T cell activation has led to solubilisation of lamina propria proteoglycans. Tissue destruction and loss of anionic residues are inhibited in a dose dependent fashion by dexamethasone, and by the protease inhibitor, alpha 2 macroglobulin. CONCLUSIONS: Proteolytic degradation of the lamina propria may therefore be a mechanism by which T cell hypersensitivity injures the intestinal mucosa.
Authors: Celso L R Belmiro; Heitor S P Souza; Celeste C S Elia; Morgana T L Castelo-Branco; Flavia R Silva; Rosane L Machado; Mauro S G Pavão Journal: Int J Colorectal Dis Date: 2005-01-20 Impact factor: 2.571
Authors: Daniela De Stefano; Maria Chiara Maiuri; Barbara Iovine; Armando Ialenti; Maria Assunta Bevilacqua; Rosa Carnuccio Journal: J Mol Med (Berl) Date: 2005-11-12 Impact factor: 4.599
Authors: Andrew M Veitch; Lisa M Higgins; Mona Bajaj-Elliot; Michael J G Farthing; Thomas T MacDonald Journal: Int J Exp Pathol Date: 2003-06 Impact factor: 1.925
Authors: A Stallmach; F Schäfer; S Hoffmann; S Weber; I Müller-Molaian; T Schneider; G Köhne; K W Ecker; G Feifel; M Zeitz Journal: Gut Date: 1998-10 Impact factor: 23.059
Authors: Maria Chiara Maiuri; Daniela De Stefano; Guido Mele; Barbara Iovine; Maria Assunta Bevilacqua; Luigi Greco; Salvatore Auricchio; Rosa Carnuccio Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2003-07-04 Impact factor: 3.000