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Biomedical subjects

U Kosecka

Publications and source records attributed to U Kosecka.

6 recordsLinked to original sources
PubMed1999

Pertussis adjuvant prolongs intestinal hypersensitivity.

BACKGROUND: Immediate hypersensitivity reactions are a hallmark of allergic disease, and result in the clinical features of food allergy, hayfever, and atopic asthma. The mechanism by which an individual becomes sensitized to an ingested or airborne allergen is not clear, however exposure to bacteria or bacterial products that act as adjuvants may be a contributing factor. The purpose of this study was to examine the role of pertussis toxin (PT) in inducing intestinal hypersensitivity reactions, particularly the ability of the adjuvant to prolong the sensitization. METHODS: Rats were sensitized to ovalbumin (OA) by injection of OA alone or with 50 ng PT. Secretory responses to OA challenge and nerve stimulation were assessed in jejunal tissues mounted in Ussing chambers. RESULTS: Jejunal segments from rats sensitized to OA alone responded to antigen challenge with ion secretion, but sensitization was transient in that specific IgE titers and responses to luminal antigen disappeared by 14 days. In contrast, co-administration of 50 ng PT with OA resulted in long-lasting sensitization. Secretory responses to both luminal and serosal OA challenge were present 8 months after primary immunization. Enhanced secretory responses to nerve stimulation, increased mucosal mast cell numbers, as well as elevated IgE titers were also induced and may have contributed to the overall responsiveness of the intestine to antigen challenge. CONCLUSIONS: Our findings indicate nanogram quantities of PT, when administered with a food protein, result in long-term sensitization to the antigen, and altered intestinal neuroimmune function. These data suggest that exposure to bacterial pathogens may prolong the normally transient immune responsiveness to inert food antigens.

Adjuvants, Immunologic↗
PubMed1994

Strain-related difference in susceptibility to anaphylactic shock correlates with measures of spontaneous activity.

The onset and severity of anaphylactic reactions in the rat have so far been related to Pavlovian conditioning, previous exposure to stress, and pretreatment with opioid agonists and antagonists. In this study, we compared two strains of rats derived from the same genetic pool (one outbred, Wistar, and one inbred, Wistar-Kyoto) for their susceptibility to anaphylactic shock (AS). In Experiment 1, baseline differences in the overt behavior of the two strains were established. In Experiment 2, following sensitization to ovalbumin, rats of both strains were challenged with antigen by either the intraperitoneal or the intragastric route. Wistar-Kyoto rats were more susceptible to the induction of AS as evidenced by a more pronounced drop in rectal temperature and greater intensity of clinical signs, although there was no evidence for strain-related differences in IgE titres. Experiment 3 replicated and extended the findings of Experiment 2. Again, Wistar-Kyoto rats were found to be more susceptible to the induction of AS. In addition to a greater drop in rectal temperature and intensity of clinical signs, more pronounced changes in gut function were found in the Wistar-Kyoto strain. This was indicated by an elevation of basal short-circuit current (an indication of the transport tone of the tissue mounted in the Ussing chambers). Most importantly, there was a strong linear relationship between measures of overt behaviour and various physiological indices of AS. This finding indicates that the same genetic basis may be responsible for the observed strain-related differences in behavior and susceptibility to AS, and that variations in nonimmunological factors of mast cell activation may also contribute to the observed differences in the susceptibility to anaphylactic reactions.

Anaphylaxis↗
PubMed1994

Pertussis toxin stimulates hypersensitivity and enhances nerve-mediated antigen uptake in rat intestine.

We previously reported that intestine from rats sensitized to ovalbumin (Ova), using Bordetella pertussis vaccine as adjuvant, demonstrated a rapid secretory response [increase in short-circuit current (Isc)] to Ova upon secondary challenge. Here, we examined the role of pertussis toxin, the active component of the vaccine, in the response. Sensitization of Sprague-Dawley rats by intraperitoneal injection of recombinant wild-type pertussis toxin (wPT) plus Ova enhanced intestinal responses (at day 14: approximately 20-fold for luminal antigen, approximately 2.5-fold for serosal antigen) compared with rats sensitized by injection of Ova alone. In contrast, sensitization with an enzymatically inactive mutant pertussis toxin (mPT, different in two amino acids) produced no significant effect. Ova-specific immunoglobulin (Ig) E and IgG2a antibodies and greater numbers of mucosal mast cells were documented in wPT-sensitized rats. In addition, the Isc response to electrical transmural stimulation of nerves in intestinal preparations was significantly augmented. Neurotoxin inhibited the secretory response to luminal but not serosal antigen. Immunophysiological stimulation by wPT was still evident 8 mo postsensitization. Our studies indicate that pertussis toxin causes long-lasting hypersensitivity to coadministered antigens, involving increased production of reaginic antibodies, hyperplasia of mucosal mast cells, and enhanced neurally mediated uptake of antigen across the intestinal epithelium. These findings suggest a potential role for bacterial products in the development of immunophysiological reactions to ingested antigens.

Animals↗
PubMed1994

Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine.

Wistar-Kyoto rats were subjected to 4 h restraint stress (RS) or cold restraint stress (CRS), and jejunal tissues were examined in Ussing chambers for alterations in transport functions compared with tissues from unstressed control rats. The baseline short-circuit current (Isc) was significantly elevated in tissues from RS (approximately 50%) and CRS (100%). Substitution of Cl- eliminated the abnormality, suggesting that stress stimulates Cl- secretion. Electrical transmural stimulation of enteric nerves caused a transient increase in Isc in all tissues. The magnitude of this response was significantly less in tissues from CRS than from control rats; however, the ability of the epithelium to secrete in response to exogenous stimulation with bethanechol or vasoactive intestinal polypeptide was unimpaired, implicating a neural change. Tissue conductance was higher in jejunum from RS and CRS rats than from controls. Increased intestinal epithelial permeability in stressed rats was confirmed by significantly greater fluxes of the inert radiolabeled probes, [3H]mannitol and 51Cr-labeled EDTA. No structural changes were observed. We conclude that acute stressors have profound effects on intestinal epithelial physiology, stimulating ion secretion and reducing barrier function.

Acute Disease↗
PubMed1992

Antigen-mediated effects on epithelial function.

In summary, immediate hypersensitivity reactions to luminal antigens occur in the intestine and result in pathophysiology including increased permeability and ion secretion. The mechanism involves activation of mast cells with neural amplification (FIG. 5). Released mediators/neurotransmitters may act independently or synergistically on the epithelium to elicit Cl ion secretion. In addition, a cyclooxygenase product of arachidonic acid metabolism, possibly of mesenchymal cell origin, may be a common mediator. However, additional effector cell(s) besides mast cells are undoubtedly involved. This system demonstrates undeniably the concept of neuro-immuno-physiology of gut mucosa.

Animals↗