Studies on the pathogenesis of early lesions in Crohn's disease : Clinical and experimental investigation

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1. Clinical investigationTo clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease, 10 patients with this disease were studied by magnifying colonoscopy, electron microscopy, and immunohitochemical examination. As a result, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy showed surface erosions 150-120mum in size. Correlation of scanning and transmission electron microscopy revealed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was more strongly expressed in the entire inflamed colonic mucosa in the active stage of Crohn's disease than in the remission stage. Therefore, the red halo appearance surrounding lymphoid follicles seems to preced visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE.2. Experimental investigationTo charac … More teriza early changes in both cryptal proliferation and expression of growth factors in indomethacin-induced small intestinal damage, scanning electron microscopic findings, cryptal proliferation (using immunohistochemical staining for Brd U), and intestinal mRNA expression of TGF-beta_1, IGF-1, HGF,and NGF (using RT-PCR) were investigated in rats which were received 24 mg/kg of intracolonic indamethacin. Scanning electron microscopy showed that the villi in the mid-small intestine was distorted with tortuous fashion at an hour. Cryptal proliferation in the mid-small intestine was not altered at 2 hour whereas it was decreased at all sites after 5 hours. IGF-1 and HGF expression became obvious at 6 hour, while NGF could not be detected at this time point. These findings suggest that early mucosal damage induced by indomethacin is characterized by alteration of the crypt architecture without changes in crypt cell proliferation, and that changes of some growth factors may play a role in the progression of the mucosal damage. Less