Selective alteration of brush-border hydrolases in intestinal diseases in childhood

Abstract

1. Biochemical estimates of lactase, sucrase and maltase activities, carried out on intestinal biopsies appearing histologically normal, were compared with those obtained from children suffering from coeliac disease, cow's milk protein intolerance/postenteritis syndrome and the intractable diarrhoea syndrome of infancy. Lactase deficiency in these children was found to be more pronounced than sucrase or maltase deficiencies. 2. Quantitative cytochemical investigations showed characteristic disease-induced changes in the ability of enterocytes to express alpha- and beta-glucosidases, but not alkaline phosphatase activities, during migration along stunted villi. 3. Separate estimates of the time course describing hydrolase development in normal and coeliac tissue showed the initial rate of lactase appearance to be halved in coeliac patients, while that for alpha-glucosidases remained constant and that for alkaline phosphatase increased by a factor of four. Enteroblastic replacement of mature enterocytes cannot provide a general explanation for hydrolase deficiency in diseased intestine.

Developmental Regulation of Intestinal Epithelial Hydrolase Activity in Human Fetal Jejunal Xenografts Maintained in Severe-Combined Immunodeficient Mice

“…For cytochemical determination of epithelial brush border enzyme activity, 10-m frozen sections of fetal, pediatric, and xenograft intestine were incubated under initial rate conditions at 37°C, with an appropriate artificial substrate as has been described previously (28, 30 -33). When preparing assays for AP, APN, and AG, tissue sections were prefixed in formal calcium (pH 6.0), consisting of 1.1% CaCl 2 and 3.8% formaldehyde in deionized water, for 10 min at 4°C before the enzyme reactions (28,33). When determining LPH and DPPIV activity, unfixed freshly cut frozen sections were used (28).…”

“…When preparing assays for AP, APN, and AG, tissue sections were prefixed in formal calcium (pH 6.0), consisting of 1.1% CaCl 2 and 3.8% formaldehyde in deionized water, for 10 min at 4°C before the enzyme reactions (28,33). When determining LPH and DPPIV activity, unfixed freshly cut frozen sections were used (28).…”

“…1, M-O). All enzyme reactions were performed under initial rate conditions as described previously (28).…”

“…Highest levels of AP activity were measured in duodenal and jejunal fetal xenografts, where enzyme activity was comparable to that in pediatric duodenal biopsies. However, AP is differentially regulated when compared with other intestinal epithelial hydrolases during childhood enteropathy (28) and malignancy (29).…”

Diet effects on enterocyte development

“…The initial fall in lactase activity probably results from increased crypt cell proliferation. The later decline in activity possibly occurs as a secondary consequence of immune reactions operating in apparently healthy animals (Phillips et al 1987). Both dietary composition and metabolizable energy can affect enterocyte differentiation.…”