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brush b o r d e r m e m b r a n e digestive peptidase: celiac disease small intestine cytosol m e m b r a n e

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ABSTRACT. Subfraction 2R of fraction 9 from a peptictryptic-pancreatic digest of wheat gliadin is known to be toxic in vivo to celiac patients. We have found that fractions 9 and 2R inhibit the in vitro development of fetal rat intestine and the increase of enterocyte height occurring in organ culture of atrophic celiac mucosa (0.1-0.5 mg/ml medium). Other peptide fractions of the gliadin digest are devoid of such in vitro effects. Subfraction ZR, after incubation with morphologically normal small intestinal mucosa of celiacs in remission and ultrafiltration, was still very active in both culture systems at low concentration (0.1 mg/ml); on the contrary, subfraction 2R was inactivated after incubation with normal mucosa. These results are compatible with the hypothesis that there is a mucosal defect in handling gliadin peptides in celiac disease, and suggest that there is either a primary (or secondary) enzyme deficiency or some other mechanism operating in the intestinal mucosa of celiac patients in remission. (Pediatr Res 24: 233-237,1988) Abbreviation PTC, peptic-tryptic-cotazymThe toxicity of wheat in celiac disease results from the gliadin protein fraction (1-6). The ingestion of peptide mixtures obtained from wheat gluten after in vitro sequential digestion with proteolytic enzymes also induced the typical symptoms in patients affected by celiac disease (7,8). Numerous studies have been done using in vitro systems which could identify the toxic peptide(s) and the mechanism(s) of their toxic activity. The organ culture of human small intestinal biopsies has been proposed as an in vitro model of celiac disease (9, 10). Jejunal specimens obtained from patients with active enteropathy show morphological and biochemical improvement when cultured in a medium free from gliadin peptides. No improvement occurs when the tissue is cultured in the presence of gliadin peptides (1 1-21). The in vitro developing fetal rat intestine also has been demonstrated to be a suitable model for the identification of peptides Received August 10, 1987; accepted April 13, 1988. Correspondence Prof. Salvatore Auricchio, Via S. Pansini, 5, 80131-Naples, Italy.that are toxic in celiac disease. Gliadin and prolamin peptides from cereals that are toxic in celiac disease (wheat, rye, barley, and oats) are very active in inhibiting in vitro development and morphogenesis of small intestine from 17-day-old rat fetuses (22, 23).Cornell and Townley (24) fractionated a peptic-tryptic-pancreatic digest of gliadin into 10 primary fractions by chromatography on S.P. Sephadex. Fraction 9 of this digest is the most active in causing significant reduction in D-xylose absorption in celiac patients in remission (25), preventing the morphological recovery of the epithelium of the atrophic intestinal mucosa of celiac patients (26) and inhibiting the in vitro development and differentiation of the fetal rat intestine (22).Subfractions 1 and 2, obtained by QAE Sephadex chromatography of fraction 9, and the purified forms 9-1B and 9-2B also have been sho...