Lipopolysaccharide-binding protein is vectorially secreted and transported by cultured intestinal epithelial cells and is present in the intestinal mucus of mice.
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Lipopolysaccharide-binding protein (LBP) is an important modulator of the host's response to endotoxin. In a previous study, we found evidence for the synthesis of LBP by intestinal epithelial cells. In this study, we explored the polarity of LBP secretion by these cells. Polarized monolayers of Caco-2 cells were used as intestinal mucosa model. Cells were stimulated apically or basally with cytokines, and LBP secretion was analyzed. Furthermore, the presence of LBP in intestinal mucus of healthy and endotoxemic mice was studied using a mucus-sampling technique. The constitutive unipolar LBP secretion from the apical cell surface was markedly enhanced when cells were exposed to cytokines at their apical surface. However, bioactive LBP was secreted from both cell surfaces after basolateral stimulation of cells. Cytokines also influenced the secretion of the acute phase proteins serum amyloid A, apoA-I, and apoB from both surfaces of Caco-2 cells. Furthermore, transport of exogenous LBP from the basolateral to the apical cell surface was demonstrated. In line with these in vitro data, the presence of LBP in intestinal mucus was strongly enhanced in mice after a challenge with endotoxin. The results indicate that LBP is present at the mucosal surface of the intestine, a phenomenon for which secretion and transport of LBP by intestinal epithelial cells may be responsible. (+info)
The agglutinating antibody response in the duodenum in infants with enteropathic E. coli gastroenteritis.
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The agglutinating antibody responses in duodenal fluid and serum were measured serially in 15 infants with enteropathogenic E. coli gastroenteritis. Peak levels of duodenal agglutinins were recorded eight to 18 days after the onset of symptoms, and the titres fell within the next seven to 14 days. These antibodies were mainly of the IgA class but IgM antibodies were detected early in the response, especially in the youngest infants. Serum antibody responses were detected in eight patients, but they correlated poorly with the titres of intestinal antibodies. No rise in serum antibodies was found in six infants. Further studies are required to determine whether these differences are host-derived or whether they reflect different pathogenic properties of the infecting organisms. (+info)
Duodenogastric reflux and foregut carcinogenesis: analysis of duodenal juice in a rodent model of cancer.
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The incidence of esophageal adenocarcinoma is increasing rapidly. In rats, surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis is based on the reaction of physiological bile acids with nitrite to produce carcinogenic N:-nitroso amides. To test this hypothesis, duodenal juice was analyzed for endogenously formed N:-nitroso bile acids and its genotoxicity was determined. Esophagojejunostomy was performed on 15 Sprague-Dawley rats to produce duodeno-esophageal reflux. At the time of surgery and 2 and 6 weeks later, duodenal contents were aspirated and analyzed immediately. High performance liquid chromatography coupled to tandem mass spectrometry was used to detect bile acids and their nitroso derivates. Genotoxicity was assessed using a micronucleus test. The characteristic pattern of bile acid derivatives, with taurocholic acid (TCA) and glycocholic acid (GCA) as the predominant conjugates, was detected in all samples. However, even selective reaction monitoring experiments failed to demonstrate the presence of any N:-nitroso-TCA or N:-nitroso-GCA. In addition, other nitroso derivatives could not be detected in any of the samples by neutral loss experiments monitoring the loss of nitric oxide (detection limit 0.1% of the concentration of TCA). All samples were cytotoxic, but neither the preoperative nor the postoperative samples were genotoxic. Duodenal juice was cytotoxic but not genotoxic. Tumorigenesis of esophageal adenocarcinoma in the rodent model could not be linked to a specific carcinogen, especially not to nitroso bile acids. Chronic inflammation is likely to be the mechanism of carcinogenesis by duodenogastric reflux. (+info)
Localization of immunoglobulins in intestinal mucosa and the production of secretory antibodies in response to intraluminal administration of bacterial antigens in the preruminant calf.
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Immunofluorescent studies of intestinal tissues from young preruminant calves demonstrate the presence of two main populations of immunocytes synthesizing IgA and IgM. These cells had infiltrated the lamina propria of the intestine as early as 4 days of age. There was little evidence of any significant involvement of IgG1 in intestinal immune synthesis of calves at this age although activity was demonstrable in the ileum and colon of one calf. In general there were more IgG2-synthesizing cells than IgG1, but these were few compared with the main populations of IgA and IgM cells. Local antigenic stimulus to the intestinal mucosa of young fistulated calves using extracts of heat-killed Gram-negative bacteria produced antibody in the secretions over a period of approximately 3 weeks. A second administration of a similar antigenic dose produced a similar response indicating the requirement for continuous stimuli to maintain a measurable level of antibody secretion. Gel filtration and antiglobulin assays indicated that the antibacterial activity was predominantly associated with IgA and that IgM also played a significant role. Oral administration of bacterial antigens to colostrum-fed calves from 5 to 8 days of age produced a faecal antibody response, indicating that intestinal secretion could be successfully interrelated with the declining passive antibody to maintain an almost continuous level of intestinal antibody in early life. (+info)
Deletion of neutral endopeptidase exacerbates intestinal inflammation induced by Clostridium difficile toxin A.
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Toxin A (TxA) of Clostridium difficile induces acute inflammation of the intestine initiated by release of substance P (SP) and activation of the neurokinin-1 receptor. However, the mechanisms that terminate this response are unknown. We determined whether the SP-degrading enzyme neutral endopeptidase (NEP, EC 3.4.24.11) terminates TxA-induced enteritis. We used both genetic deletion and pharmacological inhibition of NEP to test this hypothesis. In wild-type mice, instillation of TxA (0.5-5 microg) into ileal loops for 3 h dose dependently increased ileal fluid secretion, stimulated granulocyte transmigration determined by myeloperoxidase activity, and caused histological damage characterized by depletion of enterocytes, edema, and neutrophil accumulation. Deletion of NEP reduced the threshold secretory and inflammatory dose of TxA and exacerbated the inflammatory responses by more than twofold. This exacerbated inflammation was prevented by pretreatment with recombinant NEP. Conversely, pretreatment of wild-type mice with the NEP inhibitor phosphoramidon exacerbated enteritis. Thus NEP terminates enteritis induced by C. difficile TxA, underlying the importance of SP degradation in limiting neurogenic inflammation. (+info)
Luminal morphology of the avian lower intestine: evidence supporting the importance of retrograde peristalsis for water conservation.
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Tissue from the lower intestine of two species of sparrow, the house sparrow Passer domesticus and savannah sparrow Passerculus sandwichensis was sectioned in an unbiased manner and examined quantitatively using stereology. The tissue was processed for light microscopy, and scanning and transmission electron microscopy to examine the extent to which microvilli enhanced the epithelial surface area of the cecae, rectum, and coprodeum. Parameters measured included individual microvillus surface area, microvilli packing density, and absolute surface area. In both species, the average surface area, packing density, and absolute surface area of microvilli decreased distally along the rectum and coprodeum. All three measured variables were not statistically significant (P > 0.05) between species. Surface area amplification on the cecae due to microvilli was low, and approximated values equivalent to distal regions of the rectum and coprodeum. In the cecae, microvilli within the savannah sparrow had a significantly higher (P < 0.05) individual surface area, packing density, and absolute surface area than in the house sparrow. The functional implications of a change in microvilli population are discussed in relation to retrograde peristalsis within the lower intestine of birds. (+info)
Intestinal enterokinase deficiency. Occurrence in two sibs and age dependency of clinical expression.
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Intestinal enterokinase deficiency in 2 sibs in described. A boy failed to gain weight and had vomiting, diarrhoea, oedema, hypoproteinaemia, and anaemia in early infancy. His duodenal juice contained very low or absent proteolytic enzyme activity, which increased markedly after addition of enterokinase. He was treated with pancreatic extract and gained weight rapidly. At 44 months of age he is normal, apart from some development delay, and no longer needs pancreatic extract. His older sister, who had had similar symptoms in early infancy but then grew normally, had the same abnormality in her duodenal juice when seen at 4 years of age. Enterokinase activity was virtually absent in the duodenal mucosa of both patients. Mucosal morphology was normal. The findings suggest that enterokinase deficiency is an inherited congenital defect and not the result of mucosal damage. Affected patients may show spontaneous improvement and normal growth after the age of 6 to 12 months. This phenomenon may be related to the decreasing growth volocity during the first 2 years of life and the concimitant decrease in protein requirements per unit bodyweight. (+info)
Effect of inhibition of gastric acid secretion on antropyloroduodenal motor activity and duodenal acid hypersensitivity in functional dyspepsia.
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BACKGROUND: Heightened visceroperception and a decreased duodenal motor response to intraduodenal acid infusion have been reported in functional dyspepsia. AIM: To investigate the effect of treatment with a proton pump inhibitor on sensorimotor impairment in 19 patients with functional dyspepsia. METHODS: Patients were assigned double-blind to pantoprazole (n=10) or placebo (n=9) treatment for 2 weeks. Antropyloroduodenal manometry was performed before and after treatment, using a 21-channel catheter, and the responses to intraduodenal infusion of 5 mL of saline and acid were assessed. Nausea, fullness and epigastric pain were scored before and after each infusion. RESULTS: Acid induced a modest duodenal motor response and suppression of antral pressure waves, not altered by either treatment. However, acid evoked isolated pyloric pressure waves after pantoprazole treatment (P < 0.02), and not after placebo. Saline induced no motor response. Acid (not saline) induced nausea, both before and after treatment in both groups (all P < 0.05). Subgroup analysis of the seven acid-hypersensitive patients (37%) showed a tendency towards a decrease in nausea in all four pantoprazole-treated patients (P=0.07), in contrast to the three placebo-treated patients (P=1.0). CONCLUSIONS: In functional dyspepsia, pantoprazole influenced the acid-induced duodenogastric feedback mechanism, but not the impaired duodenal motor response. Duodenal acid hypersensitivity was decreased to some extent. (+info)