Proteolytic degradation of intestinal mucosal extracellular matrix after lamina propria T cell activation.
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.


OBJECTIVE
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.
Pender
S L
SL
Department of Paediatric Gastroenterology, Medical College of St Bartholomew's Hospital, London.
Lionetti
P
P
Murch
S H
SH
Wathan
N
N
MacDonald
T T
TT
D046508:Culture Techniques; D005109:Extracellular Matrix / Q000187:drug effects*; D016326:Extracellular Matrix Proteins / Q000276:immunology / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects
D016326:Extracellular Matrix Proteins; D006025:Glycosaminoglycans; D011043:Pokeweed Mitogens