An in vitro model of gluten-sensitive enteropathy. Effect of gliadin on intestinal epithelial cells of patients with gluten-sensitive enteropathy in organ culture.
Jejunal biopsy specimens from patients with gluten-sensitive enteropathy (GSE) (obtained during gluten challenge) as well as from normal individuals and patients with other gastrointestinal abnormalities were cultured in vitro for 48 h in the presence or absence of a peptic-tryptic digest (P-T digest) of gliadin. In the absence of gliadin the alkaline phosphatase activity in the biopsy specimens obtained from normal control individuals increased from an initial value of 384 +/- 83 U to a 48 h value of 561 +/- 151 U (mean +/- SD) (difference significant at P < 0.01). The initial alkaline phosphatase activity of specimens obtained from patients with GSE was strikingly lower than that of normals, 117 +/- 79 U, and increased to a 48 h value of 399 +/- 203 U (difference significant at P < 0.01). The biochemical change in cultured biopsy specimens of GSE patients correlated with increases in the length and regularity of brush borders of epithelial cells as seen with the electron microscope. In the presence of a P-T digest of gliadin, the alkaline phosphatase activity of biopsy specimens of control individuals increased from an initial value of 384 +/- 83 U to a 48 h value of 578 +/- 156 U. In contrast, the alkaline phosphatase activity of biopsy specimens of patients with GSE in exacerbation showed a markedly diminished increase in activity during 48 h of culture; in this case the initial activity was 117 +/- 79 U and the final activity was 203 +/- 93 U. This inhibitory effect on increase of alkaline phosphatase activity during organ culture was specific in that a P-T digest of casein (a protein not toxic in vivo to patients with GSE) had no effect on alkaline phosphatase increases in culture. Finally, these results obtained with biopsy specimens taken from patients with GSE in exacerbation were compared with results obtained from patients with GSE in remission. Alkaline phosphatase activity of specimens obtained from the latter group of patients also increased during culture but in this instance P-T digest of gliadin in the culture medium had no significant inhibitory effect. In conclusion, the inhibitory effect of gliadin on intestinal epithelial cells in organ culture represents an in vitro model of gluten-sensitive enteropathy. Inasmuch as this effect of gliadin is not seen in cultures of specimens taken from patients in remission, it appears that gliadin is not directly toxic to GSE jejunal mucosa per se, but rather toxicity requires the participation of an endogenous effector mechanism which must first be stimulated in vivo.
Falchuk
Z M
ZM
Digestive and Hereditary Diseases Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, and Metabolism Branch, Immunophysiology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014, USA.
Gebhard
R L
RL
Sessoms
C
C
Strober
W
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D002446:Celiac Disease / Q000378:metabolism* / Q000473:pathology; D002648:Child; D004186:Disaccharidases / Q000378:metabolism; D005767:Gastrointestinal Diseases; D005903:Gliadin / Q000378:metabolism* / Q000494:pharmacology; D005983:Glutens / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D008954:Models, Biological; D009924:Organ Culture Techniques
D005983:Glutens; D005903:Gliadin; D000469:Alkaline Phosphatase; D004186:Disaccharidases