Gastric Mucosal Response Research Articles

Increased serum pepsinogen-I level predicts development of new duodenal erosion following eradication teraphy of H.pylori

Aims: Eradication of Helicobacter pylori (Hp) decreases the concentrations of serum gastrin (G) and pepsinogen (PG). However, the changes in serum level of such peptides during or just after eradication therapy have not been well investigated. In this study, we evaluated the changes in serum G and PG levels at the end of eradication therapy, and then investigated the relation to the duodenal erosion following eradication. Methods: We randomly treated 318 patients (104 female and 318 men, mean age 51 years) with abdominal symptom (109 gastric ulcer (GU), 113 duodenal ulcer (DU), 32 gastro-duodenal ulcer (GDU), and 64 atrophic gastritis (AG». Before eradication, endoscopy was performed and patients with duodenal erosion were excluded. One month after eradication, endoscopy was performed to check duodenal erosion, and Hip culture, histology, and urea breath test performed to assess Hip treatment. We determined G and PG level in sera at three time points: before eradication, at the end of eradication, and one month after eradication. Results: In 272 (85.5%) cured patients, 39 (14.3%) patients had new duodenal erosions. In 46 (14.5%) patients with unsuccessful treatment, no duodenal erosion appeared. Duodenal erosion developed in 27.3%, 10.7%, 9.1%, and 0% in the patients with DU, GDU, GU, and AG. The prevalence of duodenal erosion after Hip eradication was significantly higher (p < 0.005) in DU patients than in GU, and AG patients. In cured patients, G, PG-I, II, and IIII level one month after eradication were significantly decreased compared to those measured before eradication (p < 0.005). At the end of eradication, G and PG-I level were significantly higher than before eradication (p < 0.0001). In uncured patients, no changes were seen. In the patients with new duodenal erosions, G, PG-I, II, and IIII levels were similar to non-duodenal erosion patients before eradication and one month after eradication. However, at the end of eradication, only PG-I levels were significantly higher (p < 0.0001) than in the patients with non-duodenal erosion. Conclusions: 1. Successful Hip treatment causes a temporary high G and PG-I response at the end of eradication therapy. 2. Increased PG-I might be a kind of gastric mucosal response to H.p eradication since this temporary high level of serum PG-I is strongly associated with development of new erosions in duodenum. 3. These phenomenon strongly bring about duodenal mucosal damage by excess acid secretion and PG-I following eradication therapy.

Mechanism of prevention by capsaicin of ethanol-induced gastric mucosal injury--a study in the rat using intravital microscopy.

Capsaicin acts specifically on primary afferent neurones to release neuropeptides, including calcitonin gene-related peptide (CGRP), and prevents ethanol-induced mucosal injury. To investigate the microvascular changes in the gastric mucosa in response to ethanol using intravital microscopy to elucidate the mechanism of capsaicin-induced gastroprotection. The posterior gastric wall in the rat was secured in an observation chamber and perfused with Tyrode's solution. The microcirculation was observed through a window made by removing a limited area of smooth muscle. Ethanol (50%) applied to the mucosa constricted the collecting venules and venules but dilated arterioles. The constriction of the collecting venules resulted in mucosal congestion, which caused mucosal injury. Application of capsaicin to the mucosa dilated the arterioles but not the collecting venules or venules. Arteriolar dilation was inhibited by a CGRP antagonist, CGRP-(8-37). Prior application of capsaicin prevented ethanol-induced constriction of the collecting venules, and the action of capsaicin was inhibited by prior application of CGRP-(8-37). The results suggest that the inhibition of ethanol-induced gastric injury by capsaicin is attributable to the suppression of collecting venule constriction, via CGRP release.

The relationship between persistent secretion of RANTES and residual infiltration of eosinophils and memory T lymphocytes afterHelicobacter pylori eradication

Helicobacter pylori (HP)-infected gastric mucosa displays a conspicuous infiltration of mononuclear cells as well as neutrophils. RANTES is a potent chemoattractant peptide for memory T lymphocytes and eosinophils. RANTES protein concentration and the numbers of RANTES-, CD45RO-, and major basic protein (MBP)-positive cells were therefore evaluated in the gastric mucosa from 51 patients with HP-positive chronic gastritis before and after HP eradication and from 22 HP-negative healthy volunteers. RANTES protein concentration was significantly elevated in HP-positive cases and remained high after HP eradication. The numbers of RANTES-, CD45RO-, and MBP-positive cells were significantly increased in HP-positive cases and were well correlated with RANTES protein levels. All tended to decrease after HP eradication, but did not reach the level of HP-negative cases, even at 24 months after HP eradication. It was concluded that persistent expression and secretion of RANTES were closely related to residual infiltration of memory T lymphocytes and eosinophils, for a prolonged period after HP eradication. This seems to be an important mechanism of prolonged gastric mucosal immune response against HP infection, even after HP eradication, and of persistent mucosal damage and atrophy.

Ethanol-Related Gastric Mucosal Damage: Evidence of a Free Radical-Mediated Mechanism and Beneficial Effect of Oral Supplementation with Bionormalizer, a Novel Natural Antioxidant

Twenty-two healthy teetotal volunteers underwent gastroscopy during which biopsy samples from the antrum and body were taken for chemiluminescence assay, routine histology, and for malonyldialdehyde, xanthine oxidase and glutathione determination. Subjects were divided into 2 groups which, in a double-blind fashion, were randomly and orally given either (a) Bionormalizer 9 g at bedtime and 3 h prior examination, or (b) flavored sugar 9 g as placebo. During the second gastroscopy 40 ml of 80% ethanol were sprayed perendoscopically. Gastroscopy with biopsy was repeated 60 min later. As compared to the placebo group, subjects given Bionormalizer showed significantly reduced gastric mucosal damage at endoscopy and the histological level. When considering the placebo group, ethanol administration brought about a significant increase in the luminol-amplified chemiluminescence response in gastric mucosa as compared to the baseline value which was correlated with the histological score. The mean chemiluminescence value in the Bionormalizer group was significantly lower than in the placebo group. Ethanol ingestion brought about a significant increase in xanthine oxidase and malonyldialdehyde together with a decreased glutathione concentration. Bionormalizer significantly prevented such changes. The present data suggest that the natural antioxidant Bionormalizer when given orally promotes an effective protection against ethanol-induced gastric mucosal damage.

Changes in gastric mucosal ulcerogenic responses in rats with adjuvant arthritis: role of nitric oxide.

To examine gastric mucosal ulcerogenic responses to indomethacin and HCl/ethanol in adjuvant arthritic (AA) rats. Arthritis was induced in male Dark Agouti (DA) rats by injection of Freund's complete adjuvant (FCA) into the right hind paw. The gastric ulcerogenic response to indomethacin was markedly worsened in AA rats, depending on the degree of arthritic change. This aggravation of indomethacin-induced gastric lesions in AA rats was significantly prevented by NG-nitro-L-arginine methyl ester (L-NAME) and amino-guanidine as well as dexamethasone. In contrast, the mucosal ulcerogenic response to HCl/ethanol was inhibited in AA rats. The suppression of HCl/ethanol-induced gastric lesions in AA rats was reversed almost totally by L-NAME and aminoguanidine as well as dexamethasone and partly by indomethacin. The expression of inducible nitric oxide synthase (iNOS) mRNA was observed in the stomach of AA rats but not of normal rats. Moreover, the luminal releases of nitric oxide (NO) metabolites as well as prostaglandin (PG) E2 were significantly increased in AA rats. The gastric mucosal ulcerogenic responses were modified in AA rats, in different manners depending on the irritants; an increase in response to indomethacin and a decrease in response to HCl/ethanol. These changes may both be accounted for by increased production of NO by iNOS, and the latter is also partly related to increased production of PGs.

Involvement of Endothelin-1 in Up-regulation of Gastric Mucosal Inflammatory Responses toHelicobacter pyloriLipopolysaccharide

In this study, we investigated gastric mucosal inflammatory responses duringHelicobacter pylorilipopolysaccharide-induced gastritis by analyzing the interplay between mucosal expression of endothelin-1 (ET-1), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α). The assays conducted 4 days after intragastric dose ofH. pylorilipopolysaccharide demonstrated a pattern of acute mucosal reaction characterized by the inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by a 3.1-fold increase in the mucosal expression of ET-1 and a 9-fold enhancement in TNF-α, while the level of IL-4 showed a 20.8% decline. The results implicate ET-1 in gastric mucosal responses toH. pylori,and suggest that an increase in its level, combined with a loss of compensatory action by IL-4, may be responsible for the induction of TNF-α and triggering apoptotic events that exacerbate the inflammatory process.

Changes in Gastric Mucosal Ulcerogenic Responses in Rats with Adjuvant Arthritis: Role of Nitric Oxide.

Changes in Gastric Mucosal Ulcerogenic Responses in Rats with Adjuvant Arthritis: Role of Nitric Oxide.

THE AFRICAN ENIGMA: ANALYSIS OF THE HOST RESPONSE TOHELICOBACTER PYLORI INFECTION

121 Despite the almost ubiquitous nature of H.pylori infection in Africa there is surprisingly little peptic ulcer disease and gastric carcinoma, diseases now thought to be closely linked to such infection in the West and Far East. It is not known whether such geographical variations are due to infection with organisms of different pathogenicity or to dissimilarities in the host response. The aim of this study was to provide more detail on the gastric mucosal and serological response toH.pylori infection in the Gambia. Children with diarrhoea and malnutrition (n=24; age range 3mo-11yrs [mean age 20 mo]) and adults with dyspesia (n=11; age range 18-70 yrs [mean age 37yrs]) were eligible for entry into the study. Subjects underwent multiple gastric mucosal biopsy for histological and microbiological analysis. Western blotting was used to identify antibodies to the cytotoxin-Associated Gene A (CagA) and anti-H.pylori IgG antibodies. Gastric infection with H.pylori was common with 54% (13/24) of the children and 64% (7/11) of adults positive on either histology or culture. Using the Houston Classification of gastritis, 19/20 infected cases were suitable for analysis. A striking finding was the complete absence of an acute inflammatory response in 74% (14/19) cases and only a mild response in 3/19 and moderate response in 2/19 cases. There were no cases of severe acute inflammation and no instances of intestinal metaplasia. Similarily, gastric atrophy was observed less commonly that is reported in cases of H.pylori infection in the West and was seen in only 15% (3/19) cases. Despite the relatively mild histological responses toH.pylori infection all those with proven infection had evidence of exposure to virulent CagA-positive strains of the bacterium. This study suggests that it is differences in the host response to H.pylori rather than infection with less virulent organisms that account for the African enigma.

Impact of Helicobacter pylori (HP)-infection on heat shock protein response in gastric mucosa

Impact of Helicobacter pylori (HP)-infection on heat shock protein response in gastric mucosa

The gastric mucosal immune response of patients with H. pylori infection

The gastric mucosal immune response of patients with H. pylori infection

Effect of Sucralfate on Gastric Mucosal Inflammatory Responses Induced by Helicobacter pylori Lipopolysaccharide

Background: Helicobacter pylori

Disappearance of Gastric Mucosa-Associated Lymphoid Tissue in Coeliac Patients after Gluten Withdrawal

Background: Mucosa-associated lymphoid tissue (MALT) develops in gastric mucosa in response to chronic antigenic stimulation, such as Helicobacter pylori infection. However, reactive lymphoid follicles have been found also in the stomach of H. pylori-negative coeliac patients, suggesting that other environmental factors may be involved in MALT genesis. The aim of our study was to evaluate the effects of gluten withdrawal in H. pylori-negative coeliac patients with gastric MALT. Methods: We studied 23 H. pylori-negative untreated coeliac patients with gastric MALT. All patients underwent determination of antigliadin (AGA) and antiendomysium antibodies (EMA) and upper endoscopy with multiple biopsies in duodenum, gastric corpus, and antrum. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. All patients were started on a gluten-free diet and were re-evaluated after 12 months. To consider their adherence to the gluten-free diet we relied on direct patient questioning. Thirteen patients who had strictly adhered to the gluten-free diet constituted our study group. Ten patients who had not strictly adhered to gluten withdrawal from their diet constituted the control group. Results: Regression of MALT was obtained in 9 of 13 (69%) patients who strictly followed the gluten-free diet; in the control group MALT disappeared in 2 of 10 (20%) patients (P = 0.0361). Discussion: Disappearance of reactive lymphoid follicles in the gastric mucosa of H. pylori-negative coeliac patients after gluten withdrawal suggests that antigens related to alimentary gluten may constitute persistent stimuli for development of gastric MALT in coeliac patients.

In situ expression of cell adhesion molecules in chronic gastritis with Helicobacter pylori infection.

Helicobacter pylori infection of the stomach results in acute inflammation followed by chronic inflammation, but the mechanism is unknown. Adhesion molecules such as ICAM-1, Mac-1, and LFA-1 may help regulate interactions of immune cells and inflammatory cells. We used immunohistochemistry to locate these molecules in the gastric mucosa of patients with chronic gastritis arising from H. pylori infection. Biopsy specimens were taken from five H. pylori-negative healthy volunteers and 20 H. pylori-positive patients with chronic gastritis for immunohistochemical studies of adhesion molecules. In the gastric mucosa of patients with H. pylori-associated chronic gastritis, ICAM-1 expression was prominent in most of the vessels and inflammatory cells, such as lymphocytes and granulocytes, in the lamina propria. However, no intraepithelial lymphocytes and surface epithelial cells expressed ICAM-1. Antigen-presenting cells (APCs), such as macrophages, expressed ICAM-1 as well as HLA-DR antigen. LFA-1 and Mac-1 were strongly expressed in these immune and inflammatory cells. The number of vascular endothelial cells positive for P-selectin was also greater in H. pylori-positive mucosa. The expression of these molecules decreased remarkably after successful eradication of H. pylori. In conclusion, ICAM-1 is the predominant form among the cell adhesion molecules that are expressed in response to chronic H. pylori infection. The increased expression of ICAM-1 is linked with massive infiltration of inflammatory cells that express LFA-1 and Mac-1, and also with APCs that express HLA-DR, suggesting that ICAM-1 exerts a key role in immuno-inflammatory responses in gastric mucosa of patients with H. pylori-associated gastritis.

Gastric motility and mucosal ulcerogenic responses induced by prokinetic drugs in rats under prostaglandin-deficient conditions.

The present study was performed to examine whether gastric prokinetic drugs may induce damage in the rat stomach under normal and prostaglandin (PG)-deficient conditions. Male SD rats fasted for 18 hr were administered subcutaneously with three different prokinetic drugs such as metoclopramide (3-60 mg/kg), ondansetron (0.3-3 mg/kg), and cisapride (3-30 mg/kg). Half the number of these animals were pretreated with indomethacin (5 mg/kg) subcutaneously for induction of PG deficiency in the stomach. Administration of these drugs increased gastric motor activity in a dose-dependent manner and expedited gastric emptying at lower doses than those affecting gastric motility; the potency of the hypermotility effect was in the following order: metoclopramide = ondansetron > cisapride. None of these drugs alone caused gross damage in the stomach, although whitish rough areas were observed in the gastric mucosa along the folds. In the rats pretreated with indomethacin, however, both metoclopramide and ondansetron provoked multiple hemorrhagic lesions in the gastric mucosa. Indomethacin at this dose showed over 90% inhibition of cyclooxygenase activity without causing any damage in the stomach, and this PG-deficient effect was not affected by coadministration with the prokinetic drugs. The mucosal ulcerogenic responses induced by metoclopramide in the presence of indomethacin were significantly inhibited by prior administration of atropine (1 mg/kg) or PGE2 (300 micrograms/kg) at doses that inhibited gastric hypermotility induced by metoclopramide. These results suggest that: (1) gastric prokinetic drugs induce damage in rat stomachs under PG-deficient conditions at the doses that enhance gastric motility and emptying but not at the doses that expedite gastric emptying only, and (2) gastric hypermotility has the potential to cause gross damage in the stomach, supporting the importance of gastric motility as a pathogenic element of gastric lesions.

Mechanism of gastric hyperemic response during acid secretion in rats: relation to nitric oxide, prostaglandins, and sensory neurons.

The mechanism of gastric mucosal hyperemic response during pentagastrin-induced acid secretion was investigated in anesthetized rats in relation to prostaglandins (PGs), nitric oxide (NO), and sensory neurons. A rat stomach was mounted in an ex vivo chamber and perfused with saline or glycine (200 mM), and the mucosal blood flow (GMBF), determined by laser Doppler flowmetry, and acid secretion was measured simultaneously. Intravenous infusion with a submaximal dose of pentagastrin (60 micrograms/kg/h) caused a significant increase in GMBF as well as acid secretion. Such GMBF responses were totally attenuated when acid secretion was inhibited by omeprazole and cimetidine or when the luminal H+ was buffered by mucosal perfusion with glycine (200 mM). Tripelennamine, an H1 antagonist, did not have any affect on acid secretory and GMBF responses to pentagastrin. On the other hand, prior administration of NG-nitro-L-arginine methyl ester (L-NAME), the NO synthase inhibitor, significantly mitigated the increase of GMBF induced by pentagastrin without any influence on acid secretion, and this effect was antagonized by simultaneous administration of L-arginine. The gastric hyperemic response to pentagastrin was also significantly mitigated by indomethacin or sensory deafferentation after capsaicin pretreatment, with no effect on acid secretion, and was totally inhibited by combined treatments with indomethacin plus L-NAME in addition to sensory deafferentation. Pentagastrin infusion for 8 h did not by itself cause macroscopic damage in the stomach, but additional treatments with L-NAME and indomethacin plus sensory deafferentation provoked severe lesions in the gastric mucosa. These results suggest that the gastric hyperemic response to pentagastrin (submaximal dose) is totally dependent on H+ and that this process is mediated by endogenous NO and PGs as well as by capsaicin-sensitive sensory neurons and plays a pivotal role in maintaining mucosal integrity during acid secretion.

Cytoprotective activity in the gastric mucosa of rats exposed to carbon tetrachloride-induced liver injury.

The present study was undertaken to evaluate the cytoprotective activity in the gastric mucosa of rats subjected to CCl4-induced liver injury. Response of gastric mucosa to absolute ethanol insult or acid (pylorus ligation) after CCl4 challenge was analyzed. Intraperitoneal administration of CCl4 increased plasma AST and ALT, but liver protein and glycogen levels were decreased; in addition, gastric acid secretion was significantly increased with respect to control animals (1541 +/- 266 vs. 629 +/- 25 mu eq H+; p < 0.001). Microscopical gastric erosions were observed in 3/10 animals after CCl4 challenge. Pylorus-ligated as well as CCl4-challenged rats developed increased susceptibility to gastric lesions, compared to control (lesion indices: 4.6 +/- 0.20 vs 2.8 +/- 0.13; p < 0.05), while showing increased resistance to absolute ethanol-induced gastric damage (30.4 +/- 11.2 vs 89.7 +/- 9.7 mm, p < 0.01). PGE2 levels in the gastric mucosa were not influenced by exposure to CCl4. Ultrastructural studies revealed the presence of continuous ethanol-resistant and apparently more adherent layer of mucus in CCl4-challenged animals. Morphological evaluation revealed an increase in Alcian blue-stained mucus. A dual condition of enhanced sensitivity to HCl with increased tolerance to ethanol was observed in gastric mucosa of CCl4-treated animals. These observations could be explained by the amount and/or composition of protective mucus layer in the gastric mucosa.

Induction of Acute Gastritis and Epithelial Apoptosis by Helicobacter pylori Lipopolysaccharide

Background: The preservation of gastric mucosal homeostasis is a complex biologic process, controlled by a dynamic equilibrium of cell loss by apoptosis with that of cellular proliferation, and its abrogation is a prominent feature of Helicobacter pylori-associated gastritis. In this report, we show that H. pylori lipopolysaccharide induces histologic lesions typical of acute gastritis and that these changes are reflected in the increased epithelial cell apoptosis. Methods: The experiments were conducted with groups of rats subjected to intragastric surface epithelial application of the lipopolysaccharide at 50 and 200 µg per animal. The histologic assessment of the mucosal tissue and quantification of apoptotic epithelial cells was performed 2 and 10 days after the lipopolysaccharide treatment. Results: Histologic examination showed that H. pylori lipopolysaccharide at both doses within 2 days induced infiltration of lamina propria with lymphocytes and plasma cells, edema, hyperemia, and hemorrhage extending from the lamina propria to the surface of mucosa, and the effect persisted beyond the 10 days. The in situ DNA fragmentation assay showed that lipopolysaccharide caused a marked increase in epithelial cell apoptosis, with the numerous apoptotic cells present not only in the superficial epithelium but also deeper in the glands. The mean apoptotic index in the mucosa was 59% when assessed 2 days after the administration of the 50-µg lipopolysaccharide dose and 71.9% after the 200-µg dose, whereas in the sections assessed 10 days after the lipopolysaccharide treatment the apoptotic index averaged 46% for a 50-µg dose and 76.8% for a 200-µg dose. Moreover, the apoptotic index showed positive correlation (r = 0.71) with the grade of the induced inflammatory changes. Conclusions: Our findings demonstrate that H. pylori lipopolysaccharide can cause gastric mucosal responses typical of acute gastritis and identify the lipopolysaccharide as a virulence factor responsible for the induction of gastric epithelial cell apoptosis by H. pylori.

Tachykinin inhibition of acid-induced gastric hyperaemia in the rat.

1. Primary afferent neurones releasing the vasodilator, calcitonin gene-related peptide, mediate the gastric hyperaemic response to acid back-diffusion. The tachykinins neurokinin A (NKA) and substance P (SP) are located in the same neurones and are co-released with calcitonin gene-related peptide. In this study we investigated the effect and possible role of tachykinins in the acid-evoked gastric vasodilatation in urethane-anaesthetized rats. 2. Gastric acid back-diffusion, induced by perfusing the stomach with 15% ethanol in the presence of 0.05 M HCl, increased gastric mucosal blood flow by 60-90%, as determined by the hydrogen clearance technique. NKA and SP (0.14-3.78 nmol min-1 kg-1, infused intra-aortically) inhibited the gastric mucosal hyperaemic response to acid back-diffusion in a dose-dependent manner, an effect that was accompanied by aggravation of ethanol/acid-induced macroscopic haemorrhagic lesions. 3. The inhibitory effect of NKA (1.26 nmol min-1 kg-1) on the acid-induced gastric mucosal vasodilatation was prevented by the tachykinin NK2 receptor antagonists, MEN 10,627 (200 nmol kg-1) but left unaltered by the NK1 receptor antagonist, SR 140,333 (300 nmol kg-1) and the mast-cell stabilizer, ketotifen (4.6 mumol kg-1). 4. Under basal conditions, with 0.05 M HCl being perfused through the stomach, NKA (1.26 nmol min-1 kg-1) reduced gastric mucosal blood flow by about 25%, an effect that was abolished by SR 140,333 but not MEN 10,627 or ketotifen. 5. SR 140,333, MEN 10,627 or ketotifen had no significant effect on basal gastric mucosal blood flow nor did they modify the gastric mucosal hyperaemic reaction to acid back-diffusion. 6. The effect of NKA (1.26 nmol min-1 kg-1) in causing vasoconstriction and inhibiting the vasodilator response to acid back-diffusion was also seen when blood flow in the left gastric artery was measured with the ultrasonic transit time shift technique. 7. Arginine vasopressin (AVP, 0.1 nmol min-1 kg-1) induced gastric mucosal vasoconstriction under basal conditions but was unable to inhibit the dilator response to acid back-diffusion. 8. These data show that NKA has two fundamentally different effects on the gastric circulation. Firstly, NKA reduces gastric blood flow by activation of NK1 receptors. Secondly, NKA inhibits the gastric hyperaemic response to acid back-diffusion through an NK2 receptor-mediated mechanism. These two tachykinin effects appear to take place independently of each other since they are mediated by different receptors. This concept is further supported by the inability of AVP to mimic tachykinin inhibition of the gastric vasodilator response to acid back-diffusion.

Gastrin mediates the gastric mucosal proliferative response to feeding.

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.

Manifestations of the local gastric immune response in gnotobiotic piglets infected with Helicobacter pylori

Helicobacter pylori, a human gastric bacterial pathogen, was inoculated into gnotobiotic piglets and manifestations of the resultant gastric inflammation was analyzed by in situ immunochemistry and flow cytometric analysis of isolated lamina propria leukocytes (LPL) and peripheral blood leukocytes (PBL) recovered from infected and control piglets. Gastric mucosa tissue sections from uninfected control piglets were essentially negative for cluster differentiation- (CD-) positive leukocytes. Failure to isolate significant numbers of LPL from the gastric lamina propria confirmed this observation. A local and systemic immune response occurs in piglets after infection with H. pylori. This is manifest by the appearance of cells associated with a local immune response in gastric mucosa. In gastric tissue sections from H. pylori-infected piglets, CD4-positive leukocytes were sparse and closely associated with developing lymphoid follicles whereas the CD8-positive cellular phenotype was abundant. The latter formed a continuous band in the lamina propria just above the muscularis mucosa. Perivascular accumulations of lymphocytes in the outer muscular tunic(s) were strongly positive for expression of CD8 antigen. Class II-positive cells were prominent in CD8 lymphocytic infiltrates, developing follicles and vascular endothelia but were uniformly absent from gastric epithelia even in sites overlying areas of immunocyte proliferation and infiltration. Leukocytes possessing the monocyte and granulocyte markers were rare. Plasma cells containing IgA were common in the periphery of developing lymphoid follicles or distributed as discrete foci around individual gastric pits. Fewer numbers of IgG- and IgM-positive plasma cells were identified. When the LPL flow cytometry data were compared with the flow cytometry data obtained from PBL in these same H. pylori-infected piglets, leukocytes bearing the CD8 marker predominated in LPL whereas leukocytes bearing the CD4-reactive and MHC class II markers predominated in PBL. Finally, local ELISA antibody responses were measured in mucosal explant culture supernatants and compared with in vivo antibody levels in sera, bile, and gastric juice. Antibody activity, specific for H. pylori, was detected in supernatants and serum in all three isotypes in actively infected piglets whereas gastric juice lacked antibodies. Gastric explants prepared from piglets in which infection had been successfully eradicated failed to produce local antibody into supernatant fluids. These data support the concept that the gastric inflammation observed is mediated by local immunological events.