ovalbumin and Tracheitis

Asthma is an airway chronic inflammatory disease with significant morbidity, mortality and huge social economic burden. Previous research demonstrated that the root of Aster tataricus (RA) may have the potential to treat asthma, but the efficacy and mechanism were not clear. In this study, preliminary results in vitro showed that Fr-75 eluted from RA extract could not only completely inhibit the tracheal ring contraction raised by KCl in 20 min, but also effectively affect the tracheal ring contraction induced by KCl-, Ach- and His in a concentration-dependent manner (3.91-250 μg/mL). Further results on cells exhibited that Fr-75 could decrease the concentration of intracellular Ca

Topics: Animals; Anti-Asthmatic Agents; Aster Plant; Asthma; Bronchoalveolar Lavage Fluid; Calcium Channel Blockers; Guinea Pigs; Histamine Antagonists; In Vitro Techniques; Lung; Mice; Muscarinic Antagonists; Muscle Contraction; Myocytes, Smooth Muscle; Ovalbumin; Plant Extracts; Trachea; Tracheitis

Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor possibly involved in the pathogenesis of asthma. PAR-2 also modulates ion transport in cultured epithelial cells, but these effects in native airways are controversial. The influence of allergic inflammation on PAR-2-induced changes in ion transport has received little attention. Here, we studied immediate changes in transepithelial short circuit current (I (sc)) induced by PAR-2 activation in the tracheas of naive and allergic mice. Activation of PAR-2 with an apically added activation peptide (AP) induced a small increase in I (sc), while a much larger increase was observed following basolateral AP addition. In ovalbumin-sensitized and -challenged animals used as a model of allergic airway inflammation, the effect of basolateral AP addition was enhanced. Responses to basolateral AP in both naive and allergic mice were not decreased by blocking sodium absorption with amiloride or CFTR function with CFTR(inh)172 but were reduced by the cyclooxygenase inhibitor indomethacin and largely blocked (>80%) by niflumic acid, a calcium-activated chloride channels' (CaCC) blocker. Allergic mice also showed an enhanced response to ATP and thapsigargin. There was no change in mRNA expression of Par-2 or of the chloride channels Ano1 (Tmem16a) and Bestrophin 2 in tracheas from allergic mice, while mRNA levels of Bestrophin 1 were increased. In conclusion, basolateral PAR-2 activation in the mouse airways led to increased anion secretion through apical CaCC, which was more pronounced in allergic animals. This could be a protective mechanism aimed at clearing allergens and defending against mucus plugging.

Topics: Amiloride; Animals; Asthma; Benzoates; Bestrophins; Chloride Channels; Eye Proteins; Hypersensitivity; Indomethacin; Ion Channels; Male; Mice; Mice, Inbred BALB C; Niflumic Acid; Oligopeptides; Ovalbumin; Receptor, PAR-2; Thiazolidines; Tracheitis

Eucalyptol, also known as 1,8-cineole, is a monoterpene traditionally used to treat respiratory disorders due to its secretolytic properties. In addition to its myorelaxant effects, it also has anti-inflammatory actions in vitro. In this study, we aimed to evaluate the efficacy of acute treatment with 1,8-cineole on reducing airway inflammatory parameters. Ovalbumin (OVA)-sensitized guinea pigs were submitted to antigenic challenge (OVA) with or without pre-treatment with a single dose of 1,8-cineole administered by inhalation. Airway inflammatory parameters were reduced or absent in 1,8-cineole-treated animals as compared with untreated guinea pigs. Acute treatment with 1,8-cineole impaired the development of airway hyperresponsiveness to carbachol in isolated tracheal rings. Levels of the pro-inflammatory cytokines TNFα and IL-1β was lower in bronchoalveolar lavage fluid (BALF) of 1,8-cineol-treated guinea pigs than in untreated animals. 1,8-Cineole impaired the OVA-induced increase of the myeloperoxidase activity in BALF. 1,8-Cineole also prevented the reduction of the mucociliary clearance induced by the antigen presentation. The present investigation provides evidence that inhaled 1,8-cineole prevents hyperresponsiveness and inhibits inflammation in airways of ovalbumin-challenged guinea pigs.

Topics: Administration, Inhalation; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Carbachol; Cyclohexanols; Cytokines; Eucalyptol; Guinea Pigs; Male; Monoterpenes; Ovalbumin; Tracheitis

Clinically, the subglottic and glottic mucosae may react differently, eg, during acute laryngotracheitis. In healthy rats, we showed previously that the composition of the mucosal immune system of the larynx also differs between these areas. Neutrophils, lymphocytes, and dendritic cells (DCs) are part of this mucosal immune system. In particular, DCs occupy a key function. They migrate into inflamed mucosae during the early phase of the immune response, which is normally characterized by an influx of neutrophils. Thus, they help to overcome the time lag between the innate and the adaptive immune responses. In the present study, the influx of DCs, neutrophils, and T lymphocytes into the subglottic and glottic mucosae of rats was examined at different time points after challenge with a broad spectrum of stimuli such as dead Moraxella catarrhalis, viable Bordetella pertussis, viable Sendai virus, and the soluble protein ovalbumin. The number of DCs increased rapidly after the application of the antigens. This increase was as rapid as the increase in neutrophils. Depending on the kind of antigen, their number in the mucosa increased up to 1,000 cells per 0.1 mm2 (Sendai virus). The comparison of different mucosal areas shows that an overwhelming number of immunocompetent cells entered the subglottic mucosa, whereas only a few cells migrated into the adjacent glottic mucosa. In conclusion, after inhalation of different kinds of antigens, the subset of immunocompetent cells investigated in this study entered the laryngeal mucosa in high numbers. The number of DCs entering the laryngeal mucosa was higher than the numbers of the other immune cells investigated. This finding underlines their function as first-line sentinels of the mucosal immune system of the larynx. The observation that the number of cells entering the laryngeal mucosa is location-dependent indicates the ability of adjacent laryngeal regions to react differently. This is similar to the clinical observation of a selective subglottic reaction during acute laryngotracheitis.

Topics: Acute Disease; Animals; Antigens, Viral; Bordetella Infections; Bordetella pertussis; Dendritic Cells; Glottis; Immunohistochemistry; Laryngeal Mucosa; Laryngitis; Moraxella catarrhalis; Neisseriaceae Infections; Neutrophils; Ovalbumin; Rats; Respirovirus Infections; Time Factors; Tracheitis

The majority of airway sensory innervation originates from afferent neurons whose somata reside in vagal (nodose and jugular) ganglia. Using guinea pigs immunized with chick ovalbumin, we have discovered that airway inflammation provokes phenotypic changes in the tachykinin responsiveness of nodose neurons. Bath application of substance P (SP; 0.1 to 10 microM) to nodose neurons isolated from guinea pigs with normal uninflamed airways did not elicit measurable changes in resting electrophysiological properties. In sharp contrast, 80% of nodose neurons isolated 24 h after in vivo aerosolized antigen challenge of the airway were depolarized by 100 nM SP. Inhalation of a nonantigenic protein did not evoke the expression of SP responses. Pharmacological analysis revealed that SP responses unmasked by airway inflammation were mediated by neurokinin-2 (NK-2) tachykinin receptors. There are several potential mechanisms for transduction of an "unmasking signal" from the inflamed airway to vagal afferent somata. The vagus nerve may relay the signal, either through anterograde transport and/or nerve impulse activity. Alternatively, a signal generated by airway inflammation may be carried by the circulation to the nodose ganglia. Unilateral vagotomy significantly reduced the percentage of SP-responsive neurons compared with intact controls, suggesting that the vagus nerve is required for unmasking of NK-2 responses.

Topics: Animals; Antigens; Benzamides; Disease Models, Animal; Guinea Pigs; Male; Membrane Potentials; Microscopy, Electron, Scanning; Neurokinin-1 Receptor Antagonists; Ovalbumin; Patch-Clamp Techniques; Piperidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Substance P; Trachea; Tracheitis; Vagotomy; Vagus Nerve

To elucidate whether immunoglobulin (Ig) E or IgG are involved in the murine asthma model, we compared the pathogenic features of mice that were high IgG responders (C3H/He) with mice that were high IgE responders (BALB/c) after intratracheal instillation of diesel exhaust particles (DEP) and ovalbumin sensitization. Both mouse strains received DEP intratracheally once a week for 5 weeks. After the second injection of DEP, ovalbumin and aluminium hydroxide were injected intraperitoneally. After the last DEP administration, the mice were challenged by exposure to an aerosol of ovalbumin. DEP caused increased IgG1 production and airway hyperresponsiveness after ovalbumin sensitization in C3H/He mice, although IgE production did not change in either strain. Furthermore, in C3H/He mice, the number of eosinophils and goblet cells in the bronchial epithelium, and the expression of interleukin-5 and interleukin-2 were increased by DEP and ovalbumin treatments. In contrast, the pathogenic changes in BALB/c mice were weak, even though the same protocol was used. In conclusion, murine strain differences in response to air pollutants and allergens seem to be related to antigen-specific immunoglobulin G1 production and cytokine expression in the lungs.

Topics: Aerosols; Animals; Cytokines; Gasoline; Immunization; Immunoglobulin E; Immunoglobulin G; Injections, Intraperitoneal; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mucus; Ovalbumin; Respiratory Hypersensitivity; Species Specificity; Trachea; Tracheitis; Vehicle Emissions

The challenge of previously sensitized guinea pigs with aerosolized ovalbumin resulted in impairment of the beta-adrenoceptor-mediated relaxation as measured by the in vitro isometric assay of tracheas preconstricted with endothelin-1 or carbamylcholine. Numbers and affinities of beta-adrenoceptors in lung membranes of these animals were not altered under these conditions, although the antigen challenge caused an inflammatory response, as evident from the accumulation of inflammatory cells in the bronchoalveolar lavage fluids. In order to investigate the pathophysiologic role of inflammation in hyperreactive airways, isolated guinea pig tracheas were cultured with proinflammatory cytokines such as human recombinant tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), or interleukin-2 (IL-2). None of these cytokines affected the contractile response of tracheas to carbamylcholine. After preconstriction with carbamylcholine, the TNF-alpha- and IL-1 beta-pretreated tissues produced a significant reduction in the maximal relaxation induced by isoproterenol, whereas the IL-2 pretreatment had no effect. The reduction of the isoproterenol-mediated relaxation by the IL-1 beta treatment was time and dose dependent. Our present observations suggest that in vitro incubation of naive tracheas with proinflammatory cytokines is able to reproduce apparent beta-adrenoceptor impairment as seen in the airways of antigen-challenged guinea pigs of asthma model.

Topics: Animals; Carbachol; Cytokines; Female; Guinea Pigs; Interleukin-1; Interleukin-2; Isoproterenol; Muscle Contraction; Muscle Relaxation; Organ Culture Techniques; Ovalbumin; Receptors, Adrenergic, beta; Trachea; Tracheitis; Tumor Necrosis Factor-alpha