FUNCTIONAL MATURATION OF HUMAN DEVELOPING PARIETAL CELLS

Abstract

71 Parietal cells (PC) appear in the foetal stomach, by 11 weeks of gestation, and at this stage they are able to secrete intrinsic factor (IF). Unfortunately, we know little about IF proprieties during development of human gastrointestinal tract. In order to study IF secretion in relation to morphological and functional aspects of PC, human embryo-foetal (6-10 week-old) were engrafted in recipient nude and SCID mice. By using microsurgical methods, transplant-stomachs were engrafted (i) inside a peritoneum pouch (n = 15), and (ii) on the stomach and oesophagus (n = 15). At 1, 2 or 3 months, mucosal PC were analysed by haematoxylin-eosin staining, immunohistochemistry (IHC) and ultrastructure. Acidic and IF secretion were determined in the gastric juice. After separation, IF was characterised by liquid isoelectrofocalisation, after treatment with N-glycanase and neuraminidase or not. No PC is usually detected in mucosa of 6-10 week-old human embryo-foetal stomachs. In contrast, PC were identified by light and electron microscopy after a one-month transplantation. Expression of IF and H+/K+-ATPase was revealed by IHC, irrespectively to graft sites and delays. After 1, 2 or 3 months of transplantation, pH was 6.9 ± 1.2, 4.9 ± 2.1 and 3.4 ± 2.4 in specimens engrafted inside peritoneum pouch, and respectively 3.6 ± 2.0, 2.9 ± 1.6 and 2.4 ± 0.7 in host stomach-grafts. IF concentrations (n = 30) were not affected by graft site and duration : 27 ± 17 pmol/ml (6-55). IF proteins isoelectric point was 4.3 ± 0.2 (n = 3) for specimens engrafted on host stomach. No acidic IF proteins were found before 3 months of transplantation inside the peritoneum pouch. Treatment with glycosidases demonstrated that acidic IF proteins contained sialic acid, thus providing a useful glycosylation as seen in adult IF. Our results suggest that IF and H+/K+-ATPase mucosal expression, as well as asialo intrinsic factor secretion, appeared in the earlier stages of PC differentiation. In contrast, sialilation of IF and acidic secretion appeared when PC were fully maturated and functional. It could be also hypothetised that during human gastrointestinal tract development, foetus may use B12 vitamin contained in amniotic fluid.