Using a technique of tolerization, a murine monoclonal antibody (MAb 2E8) has been raised which displays regional differences in reactivity in the epithelium of the normal human colon and increased reactivity in active ulcerative colitis. MAb 2E8 (IgG1) was highly colon‐specific and gave higher immunoperoxidase staining scores in the proximal colonic mucosa compared with paired rectal sections (P<0·02). Expression of the antigen reactive with MAb 2E8 was enhanced in active ulcerative colitis compared with quiescent ulcerative colitis (P<0·05) and normal controls (P<0·001). Western blotting and indirect immunofluorescent screening on transfected cell lines established that MAb 2E8 was reactive with carcinoembryonic antigen (CEA). This is the first demonstration of regional differences in the expression of CEA in the normal colon and indicates upregulation of this molecule in active ulcerative colitis.
The mucosa of the functioning pelvic ileal pouch undergoes loss of villous height and an increase in crypt cell proliferation as an adaptive response to its new luminal environment. These changes can occur in the absence of inflammation and could be mediated by growth factors such as transforming growth factors alpha and beta1 (TGFα and TGFβ1). Expression of TGFα and TGFβ1 messenger RNA (mRNA) and protein was determined by in situ hybridization and immunohistochemistry in sections of terminal ileum taken at the time of pouch formation and of subsequent pouch biopsies from 14 patients (total of 90 specimens). Crypt cell proliferation was assessed using the monoclonal antibody MIB‐1. As ileal pouch mucosa underwent loss of villous height and crypt hyperplasia, epithelial expression of TGFα mRNA and protein decreased. In contrast, TGFβ1 mRNA and protein were abundant in both normal and flat mucosa. Epithelial expression of TGFβ1 protein was maximal in flat, inflamed biopsies. These results suggest that although altered expression of TGFα and TGFβ1 mRNA and protein may play some part in the regulation of the adaptive response in ileal pouch mucosa, TGFα does not have a direct, positive role in the regulation of crypt cell proliferation.
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