Abstract
Summary: A peptic-tryptic-cotazym (PTC) digest of a crude wheat gliadin preparation was obtained under experimental conditions simulating in vivo protein digestion and then fractionated into 10 peaks by ion-exchange chromatography. PTC-gliadin digest and one of its subfractions (coded as fraction 9 according to its elution pattern) were very active in inhibiting in vitro development and morphogenesis of small intestine from 17− and 18-day-old rat fetuses, whereas they were harmless for the culture of jejunum from 21-day-old fetuses. PTC-digest also induced extensive tissue degeneration and necrosis of in vitro cultured small intestinal mucosa from patients with active celiac disease (gluten-induced entheropathy), but did not cause any detectable effect on histolog-ically normal human small intestinal mucosa. Some wheat albumin and gliadin fractions were also tested on in vitro developing small intestine from 17-day-old rat fetus. Among all the tested protein fractions, only one gliadin fraction (coded as α10-gliadin from its gel electrophoretic mobility) exhibited a toxic effect; morphologic alterations induced by α10-gliadin were similar to those induced by PTC-digest and fraction 9.
Speculation: Peptides obtained from wheat gliadins under in vitro conditions simulating protein digestion by humans as well as whole wheat gliadin are very active in damaging in vitro developing jejunum from 17− and 18-day-old rat fetuses, but have no toxic effect on the culture of jejunum from 21-day-old rat fetus. The transient character of such an effect is suggestive of a protective mechanism against the toxic protein components from wheat, associated with the age-dependent maturation of rat intestinal mucosa. It is speculated that also human normal intestine develops with maturation similar specific detoxifying mechanisms and that wheat gliadin and gliadin-derived peptides might exert a toxic action when human intestinal mucosa is not yet fully mature (i.e., during early extrauterine life) or when adult human mucosa regresses towards immature steps of development (i.e., in intestinal diseases with mucosal atrophy).
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Ritis, G., Occorsio, P., Auricchio, S. et al. Toxicity of Wheat Flour Proteins and Protein-Derived Peptides for In Vitro Developing Intestine from Rat Fetus. Pediatr Res 13, 1255–1261 (1979). https://doi.org/10.1203/00006450-197911000-00010
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DOI: https://doi.org/10.1203/00006450-197911000-00010
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