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Biomedical subjects

E Telemo

Publications and source records attributed to E Telemo.

49 records · Page 3Linked to original sources

Induction of IgE antibodies and T-cell reactivity to ovalbumin in rats colonized with Escherichia coli genetically manipulated to produce ovalbumin.

The immune response to ovalbumin (OA) and the bacterial antigens, lipopolysaccharide (LPS) and fimbriae were studied in conventional rats colonized from birth with an Escherichia coli strain producing OA. The colonized rats had developed IgE antibodies against OA, but not against the fimbrial or the LPS antigens from the E. coli at 2 months of age. At this time all rats were primed with OA given intracutaneously in Freund's complete adjuvant. Two weeks later the colonized rats showed a 35% greater delayed-type hypersensitivity (DTH) reaction to OA, measured as ear swelling, than the controls. Thus bacteria carrying antigens resembling potential allergens might aggravate, or participate in the induction of allergic symptoms. In addition such bacteria could be efficient vaccine vectors in protection against parasites. The study illustrates the importance of the mode of antigen presentation for the subsequent immune response.

Animals↗

Dietary antigen handling by mother and offspring.

Sows were fed ovalbumin (OvA) as a novel protein antigen either throughout gestation and lactation (G + L) or during lactation only (L). This resulted in a significant uptake of OvA into blood, colostrum and milk along with a specific IgG response. In piglets from the G + L group, OvA and antibodies to OvA were detected in serum after ingestion of colostrum. In a large proportion of these piglets OvA was still detected at 3 weeks of age. In the L group a significant proportion of the piglets responded to OvA whilst still suckling their mother. At 3 weeks of age all piglets were weaned onto an egg-based diet. A similar uptake of OvA was seen in all piglets but there was no response to OvA in the G + L piglets. In piglets from sows fed only during lactation, however, a rapid IgG anti-OvA response and signs of diarrhoea were seen. The results suggest that factors of immunological importance are passed over from mother to offspring and it is proposed that immunological experience of dietary antigens by the mother is important for a 'safe' tolerance induction in her offspring.

Animals↗

The uptake of fluorescein-conjugated dextran 70,000 by the small intestinal epithelium of the young rat and pig in relation to macromolecular transmission into the blood.

The macromolecular transmission from the intestinal lumen into the circulation, and its cessation (intestinal closure), were investigated in young rats and pigs in relation to the enterocytes ability to internalize macromolecules. After gavage feeding of FITC-labelled dextran 70,000 (FITC-dextran) and bovine serum albumin (BSA), the uptake of FITC-dextran into the enterocytes was examined by fluorescence microscopy, and the intestinal transmission of both markers was estimated from their blood serum concentrations. In both preclosure rats (14-days old) and piglets (newborn, unsuckled), high serum concentrations of the markers were correlated with the presence of highly fluorescent enterocytes. Although the transmission of the markers to the blood had ceased in postclosure suckling pigs (24-h old), the enterocytes showed a high fluorescence, indicating that the cellular uptake of FITC-dextran was still high. In the 6-days old piglets, only the distal part of the intestine showed uptake of FITC-dextran. In postclosure rats (21- and 30-days old) and in pigs 4-8 weeks old, no fluorescence in the enterocytes and only trace amounts of markers in the serum could be detected. These results reflect differences in the closure process between the species. In the rat, closure is likely to be due to a decrease in the endocytotic activity of the enterocytes, whereas closure in the pig is related to a cessation of the passage of internalized material into the blood (transcytosis).

Animals↗

Development of phospholipase A2 and lysophosphatidylcholine metabolising enzyme activities in the neonatal rat intestine.

We have studied the development of phospholipase A2 (PLA2) and lysophosphatidylcholine (lysoPC)-metabolising enzyme activities in the neonatal rat intestine and its relation to the intestinal permeability of macromolecules. The permeability was determined by feeding young rats a mixture of bovine serum albumin, bovine immunoglobulin G and fluorescein-isothiocyanate-conjugated dextran 70,000, and analysing the serum concentrations after six hours. The animals were then killed and the intestinal mucosa was homogenised and assessed for PLA2 and lysoPC-metabolising enzyme activities. The intestine was 'open' to the macromolecules in 14 day old animals, but 'closed' in 22 and 32 day old animals and in 14 day old rats treated with cortisone acetate on day 10, 11, and 12 postpartum. The activity of PLA2 (at pH 6 and 2 mM Ca2+) was higher in 32, 22, and cortisone treated 14 day old animals, than in untreated, 14 day old animals. Incubation of 14C-acyl-lysoPC with mucosa from 14 day old rats did not change the radioactivity pattern as shown by thin layer chromatography, whereas after incubation with mucosa from 22 or 32 day old animals all the radiolabel was found in free 14C-fatty acid and in 14C-phosphatidylcholine. These findings indicate that mucosal PLA2 activity increases during intestinal maturation and that the mucosa acquires the ability to acylate and deacylate lysoPC when it is 'closed' to macromolecules.

Animals↗

Intestinal macromolecular transmission in the young rat: influence of protease inhibitors during development.

Intestinal macromolecular transmission in young rats of 10, 14, 18, 22 and 30 days of age was measured as the blood serum levels of markers 6 h after oral feeding of a solution containing bovine IgG (BIgG), bovine serum albumin (BSA) and fluorescein-isothiocyanate-labeled dextran 70,000 (FITC-D), either alone (controls) or with soybean trypsin inhibitor (SBTI) or swine colostrum trypsin inhibitor (SCTI). In the 10- and 14-day-old rats, transmission of all three macromolecular markers was high, with a preference for IgG. Transmission was greatly reduced by the age of 18 days and totally arrested for the protein markers at 22 days, with a low transmission of FITC-D remaining at 30 days of age. Addition of either of the two protease inhibitors significantly elevated the transmission of the protein markers in the rats aged 10, 14 and 18 days, while the transmission of the protease-independent marker FITC-D was unaffected. From 14 days of age, the rats have a functioning intestinal proteolysis, since only small amounts of marker proteins were left in the gut lumen 6 h after feeding, and since the addition of protease inhibitors resulted in increased amounts of undegraded proteins intraluminally. The results indicate that the increase of intraluminal proteolytic activity during development and the presence of protease inhibitors in the food are of importance for the intestinal transmission of undegraded proteins in the young rat. The Fc receptor for IgG in the enterocyte is not sufficient to maintain an optimal transmission of IgG, since the intraluminal proteolytic activity also appears to be of importance.

Animals↗

Maternal dietary antigens and the immune response in the offspring of the guinea-pig.

Guinea-pig dams and their litters were raised on either a cow's milk protein-containing diet (MCD) or a milk-free diet (MFD). At 8 weeks of age all litters were challenged i.p. with 50 micrograms milk whey-protein concentrate (V67) and 100 mg A1(OH)3 in saline. The immune response was estimated 2 weeks later as the serum IgG antibody titres against V67, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) using enzyme-linked immunosorbent assay (ELISA) and the tracheal Schulze-Dale response to these antigens. Feeding milk protein antigen to dams from birth and during pregnancy induces antigen-specific hyporesponsiveness (tolerance) in their offspring, despite no direct contact between the offspring and the milk proteins. Tolerance seems to be induced by the antigen itself since withdrawal of the MCD 10 days before delivery reduced tolerance in the offspring. No tolerance was produced in the offspring of dams fed the antigen from 3 months of age (adult). beta-LG appears to be a major antigen in milk whey while alpha-LA is a minor one since there was almost no antibody or tracheal response to alpha-LA in any of the animals tested. The results indicate that maternal antigen experience and antigens present during pregnancy are important for the subsequent immune response to these antigens in offspring.

Animals↗

The passage of orally fed proteins from mother to foetus in the rat.

Pregnant rats were orally fed with a mixture of bovine IgG, bovine albumin, ovalbumin and beta-lactoglobulin. Using immunoprecipitation methods, these proteins were detected in the maternal blood serum, urine and uterine fluids, and also in the foetal blood serum and the amniotic fluid. The results imply that a variety of dietary proteins, still immunoprecipitable, are able to cross the materno-foetal barriers to be detected in the foetal circulation, where they may influence the maturation of the immune system of the foetus.

Animals↗

Proteolytic activity as a regulator of the transmission of orally fed proteins from the gut to the blood serum in the suckling rat.

14-day-old rats were orally fed with porcine colostrum or serum having a low or high activity of protease inhibitors (i.e., sow colostrum trypsin-chymotrypsin inhibitor or soybean trypsin inhibitor). The uptake of undigested porcine albumin and IgG to the blood serum of these rats was studied 4 h after feeding. The effect of the exclusion of proteases to the intestinal lumen by means of pancreatic duct ligation prior to feeding was also studied. The results from these feeding experiments in the presence of protease inhibitors or in the absence of pancreatic proteases agreed well. It was concluded that for the sucking rat the intraluminal proteolytic activity in the gastrointestinal tract is a regulator for nonselective protein uptake, as represented by albumin, while the selective absorption of IgG was unaffected.

Animal Population Groups↗

Effects of adrenergic beta-blockers and a membrane stabilizing agent on ouabain-induced cardiac arrhythmias in anaesthetized guinea pigs.

The antiarrhythmic effects of dl'propranolol, d-propranolol, metoprolol and lidocaine against ouabain-induced cardiac arrhythmias were studied. It was found that contrary to earlier findings in the dog, the effects of the adrenergic beta-blockers against ouabain-arrhythmias in guinea pigs were due to beta-blocking activity and not the membrane-stabilizing activity of the compounds. The cardioselective beta-blocker, metoprolol, was more or equally effective as dl-propranolol against ouabain-induced arrhythmias in guinea pigs.

Adrenergic beta-Antagonists↗

Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.

In humans, the small intestinal epithelial cells (IEC) have a high constitutive expression of MHC class II (MHC II), and contains lysosomes. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes. This suggests a role for the IEC in antigen processing and presentation either directly or indirectly by the production of exosomes. However, the presence and localisation in the IEC of other key molecules involved in this process has not been studied previously. In the present work, we have investigated small intestinal biopsies from healthy adults and the HT29 IEC cell line with monoclonal antibodies against molecules involved in the antigen processing/presenting systems and molecules typically found on exosomes derived from professional APCs and IECs. Immunohistology was performed to study the expression and localisation of MHC II (HLA-DR), HLA-DM, MHC I (HLA-ABC), CD1d, Invariant chain, Lamp-1, CD68, CD63, B7.1, B7.2, ICAM-1, Cathepsin D/S/L and the IEC specific marker A33 in the IECs. We found that the IECs from the biopsies constitutively express MHC II, HLA-DM, MHC I, Invariant chain, Lamp-1, CD 68, CD63 and A33, and these markers were also found in the IFN-g treated HT-29 cells. All these molecules were found apically in the IECs of the biopsies, localised mainly in vesicular structures. Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. CD1d, B7, ICAM-1, CD9 and cathepsin D and L were absent in the IEC compartment, but cathepsin S showed a relatively weak staining in the apical part of the IEC. The staining pattern and the morphological localisation of these markers suggest a prominent antigen processing/loading and trafficking compartment, and a possible baso-lateral release of exosomes in the normal human IEC.

Adult↗

Food allergens transformed into tolerogens.

Antigen presentation determines immunologic outcome, and by modifying the presentation of allergen to the host one can prevent an allergic response. Under certain conditions, covalent linkage, of ovalbumin to rat IgG, a molecule already tolerated by the host, can make a protein-IgG conjugate which down-regulates the immune response to this food allergen. The suppression is allergen specific. It affects both T and B cell immune responses. Administration of allergens linked to isologous IgG may provide a novel strategy for allergy prevention.

Allergens↗

Transfer of orally or intravenously administered proteins to the milk of the lactating rat.

Lactating rats were given a test solution containing various marker proteins via oral or intravenous routes. Using immunoprecipitation methods for the detection of ovalbumin (OvA), bovine serum albumin (BSA), and bovine gammaglobulins (BIgG) and radioimmunoassay for the analysis of beta-lactoglobulin (beta-LG), these proteins could be found in the blood serum and the milk of the rat 6 h after administration. A specific distribution pattern between the serum and the milk was observed for each protein. The results show that orally fed dietary proteins are able to cross the gut of the lactating rat and can be found in the serum and the milk. It was also observed that oral feeding of the proteins resulted in relatively greater concentrations in the milk than did intravenous administration. This very early presentation to the young of antigenic macromolecules derived from the mother's diet might be of importance for the development of a proper immunological response to common food antigens.

Administration, Oral↗