Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa

Background and aims-Trefoil factor family (TFF) peptides and the chromosome 11p15.5 mucin glycoproteins are expressed and secreted in a site specific fashion along the length of the gastrointestinal tract. Evidence for coexpr ession of mucins and trefoil peptides has been suggested in numerous gastro intestinal mucosal pathologies. The ulcer associated cell lineage (UACL) oc curs at sites of chronic ulceration in Crohn's disease, expresses all three trefoil peptides, and is implicated in mucosal restitution. We tested the hypothesis that individual trefoil peptides are uniquely localised with spe cific mucins in the UACL and normal gastrointestinal epithelia. Methods-Expression of mucin genes in the UACL from small bowel tissue of pa tients with Crohn's disease was detected by in situ hybridisation, and loca lisation of the products by immunohistochemistry. Colocalisation of mucins and trefoil peptides was demonstrated by immunofluorescent colabelling in U ACL and normal gastrointestinal epithelia. Results-MUC5AC and TFF1 were colocalised in distal ductular and surface ele ments of the UACL and in foveolar cells of the stomach, whereas MUC6 and TF F2 were colocalised to acinar and proximal ductular structures in the UACL, in the fundus and deep antral glands of the stomach, and in Brunner's glan ds of the duodenum. MUC5B was found sporadically throughout the UACL and ga stric body. MUC2 was absent from the UACL, Brunner's glands, and stomach. M UC2 and TFF3 were colocalised throughout the large and small bowel mucosa. Condusions-The UACL has a unique profile of mucin gene expression. Coordina ted localisation of trefoil peptides and mucins in UACL and normal gastroin testinal epithelia suggests they may assist each others' functions in prote ction and repair of gastrointestinal mucosa.