CD24 is expressed in gastric parietal cells and regulates apoptosis and the response to Helicobacter felis infection in the murine stomach.

CD24 is expressed in the putative stem cells within several tissues and is overexpressed in gastric and colonic adenocarcinomas. Perturbed CD24 expression may therefore alter the response of gastrointestinal epithelia to damage-inducing stimuli that induce cancer. We have investigated the effects of CD24 deletion on gastric responses to Helicobacter felis infection and γ-irradiation using CD24-null mice. Gastric CD24 expression was determined by immunohistochemistry in C57BL/6 mice. Female CD24-null and C57BL/6 mice were infected with H. felis for 6 wk, and inflammation, proliferation, apoptosis, and parietal cell numbers were assessed in gastric tissue sections. Apoptosis and proliferation were analyzed on a cell-positional basis in stomach, small intestine, and colon of CD24-null and C57BL/6 mice following γ-irradiation. Apoptosis was also assessed in HT29 cells following CD24 siRNA transfection. Of CD24-positive cells in the gastric corpus, 98% were H(+)-K(+)-ATPase-expressing parietal cells. CD24-null mice showed more prominent gastric H. felis colonization than C57BL/6 mice but displayed a marked reduction in corpus inflammation, reduced Ki67 labeling, and less gastric atrophy 6 wk following infection. Corpus apoptosis was elevated in CD24-null mice, but this did not increase further with H. felis infection as observed in C57BL/6 mice. More apoptotic cells were found following γ-irradiation in the stomach, small intestine, and colon of CD24-null mice and following CD24 knockdown in vitro. In conclusion, CD24 is expressed in gastric parietal cells, where it modulates gastric responses to H. felis and γ-radiation. CD24 also regulates susceptibility to apoptosis in the distal murine gastrointestinal tract.

Omeprazole does not cause unscheduled DNA synthesis in rabbit parietal cells in vitro.

Parietal cells from rabbit gastric mucosa, enriched to greater than 90% purity, were used to study the effect of the H+,K(+)-ATPase inhibitor omeprazole on DNA in vitro. In this preparation, omeprazole undergoes acid-catalyzed conversion to its active form, the sulfenamide, which subsequently binds to luminal SH groups of the H+,K(+)-ATPase and thereby inhibits acid secretion. In the parietal cell fraction the S-phase inhibitor hydroxyurea (HU) decreased [3H]thymidine uptake by 40% as measured by liquid scintillation counting (LSC), presumably due to inhibition of scheduled DNA synthesis in contaminating stem cells. In the presence of HU, irradiation with ultraviolet light (UV) or treatment with the gastric carcinogen, 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) increased [3H]thymidine uptake by a factor of 5. Autoradiography of isolated, stimulated parietal cells showed that UV irradiation and MNNG treatment increased the average number of silver grains over the nuclei 18-fold and 4-fold, respectively. In contrast, treatment of histamine-stimulated parietal cells with omeprazole or ranitidine in concentrations 100 times the IC50 value for inhibition of acid secretion in the parietal cells did not increase [3H]thymidine incorporation above the control levels, measured either by LSC or by autoradiography. Extracted DNA from stimulated parietal cells treated with [3H]omeprazole or [3H]MNNG showed no binding of [3H]omeprazole but considerable binding of [3H]MNNG. It is concluded that parietal cells can undergo DNA repair, but there is no indication that omeprazole, or its acid-derived metabolites, should cause any damage to DNA, nor does it bind to DNA in its target cell, where the highest concentrations of omeprazole and its acid-derived products are found.

Induction of intestinal metaplasia in the rat gastric mucosa by local X-irradiation.

Attempts were made to learn about an optimal condition for the induction of intestinal metaplasia in the gastric mucosa. The gastric region of 5-week-old female Wistar rats was irradiated with 500 rad of X-ray daily for 6 times (Group I) or with 1,000 rad of X-ray every two days for 3 times (Group III). In addition, the effect of immunization by allogeneic stomach antigen on the intestinalization was studied in rats irradiated with 500 rad of X-ray daily for 6 times (Group II). In a group of rats (Group II) injected with allogeneic stomach antigen and X-irradiated the process of intestinalization was more accelerated as compared to that in rats treated with X-ray (Group I). The similar results were obtained in rats irradiated with 1,000 rad of X-ray 3 times (Group II). Intestinal metaplasia developed more later in the fundic gland mucosa which became usually atrophic due to the loss of parietal cell mass. There was an intimate association among the parietal cell loss in the fundic gland, a rise in pH value and the development of intestinal metaplasia. In all groups, no case of gastric adenocarcinoma was detected during observation period up to 52nd week.