Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.
We recently showed the involvement of the L-arginine/nitric oxide (NO) pathway in acid-induced duodenal mucosal bicarbonate secretion in rats. The aim of the present study was to confirm this observation in pigs by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg-1, intravenously). A duodenal segment, devoid of pancreaticobiliary influxes, was perfused with saline and the duodenal mucosal bicarbonate secretion was calculated from continuous measurements of pH and PCO2. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO. Luminal acidification with 30 mM hydrochloric acid increased the output of bicarbonate as well as NO to the perfusate, by 195 +/- 45% and 106 +/- 10%, respectively. These responses to acid were markedly inhibited by adding the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could be reversed by administration of L-arginine (3 mM). The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L-arginine/NO pathway is involved in the acid-induced duodenal mucosal bicarbonate secretory response.
Nitric oxide (NO) in the gut has attracted increasing interest as a regulatory factor for a wide variety of intestinal functions. This study was performed to evaluate some methodological aspects and jejunal sources for NO synthesis. Bench side evaluations and an animal model using chloralose-anaesthetized pigs were used. Immunohistochemistry was performed on samples from pig intestine and direct measurements of intestinal NO formation were performed using intraluminal tonometry. Tonometric measurements were quantitatively accurate and with high reproducibility. A substantial NO formation was assessed which was markedly inhibited by luminal administration of the non-selective NOS inhibitor L-NAME. Intravenous administration of L-NAME also reduced jejunal NO formation but to a lesser extent. Immunohistochemistry revealed staining for the inducible type of NOS in the mucosal surface epithelium whereas endothelial and neuronal subtypes were located in deeper layers of the jejunal wall. The study argues for that the source of jejunal NO production, as measured by intraluminal tonometry, is located in close proximity with the intestinal mucosa. The NOS in this compartment is predominantly of the inducible type.
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