Absence of Nasal Blockage in a Japanese Cedar Pollen-Induced Allergic Rhinitis Model Mouse

Background: Japanese cedar pollen-induced allergic rhinitis in a guinea pig model clearly induced not only sneezing but also biphasic nasal blockage. To date, there have only been a few reports on models of murine allergic rhinitis which clearly show nasal blockage. Therefore, in order to try and develop such a model, we administered multiple dosages of intranasal pollen or purified antigen protein Cry j 1. Methods: B10.S mice were sensitized by intranasal instillations of either pollen extract or Cry j 1 twice a day for 7 days, which was adsorbed on Al(OH)3. Subsequently, once a week, the mice were given multiple intranasal instillation challenges of either the pollen suspension or Cry j 1 and the frequency of sneezing was observed after respective challenges were made. Specific airway resistance (sRaw) was measured as an indicator for nasal blockage. Cry j 1-specific IgE levels were measured using an enzyme-linked immunosorbent assay. Results: The serum Cry j 1-specific IgE level showed clear elevation only in the group sensitized by Cry j 1 + Al(OH)3 and then challenged by Cry j 1. No elevations were seen in the groups sensitized by pollen extract + Al (OH)3 followed by a pollen suspension challenge. There was an immediate increase in sneezing after challenges in all of the sensitized-challenged groups. Nevertheless, no increases in sRaw in any of the groups were detected at any of the time points during the 8 hours following the challenges. Conclusions: Cry j 1 may be more effective than crude antigens for efficient sensitization/challenge in mice. No increase in sRaw occurred, even in mice that possessed high amounts of Cry j 1-specific IgE and that exhibited sneezing

Comparative studies on nebulizers for antigen inhalation in experimental asthma

The majority of cases of allergic asthma in experimental animals have been provoked by inhalation with mist antigen. Because of the inherent inability of some species to breathe through the mouth, including guinea pigs, mice and rats, an upper airway response may be substantially involved in experimental asthma induced by antigen inhalation. With this in mind, we evaluated three types of nebulizers (a hand-made glassware pressure nebulizer (GPN), a DeVilbiss nebulizer (DN) and an ultrasonic nebulizer (UN)) with respect to their ability to adequately sensitize/challenge guinea pigs by antigen inhalation in bronchial asthma. Several solutions and suspensions, including antigen and AI(OH)3, were atomized with these three nebulizers. The results obtained were as follows: irrespective of the type of solution or suspension used, of the three nebulizers, GPN generated mists with the smallest diameter. The rank order of median diameter of the mists generated was GPN (1.6-2.1 μm) < DN (2.2-3.5 μm) < UN (4.3-4.7 μm). When Evans blue mists produced by the GPN were presented to guinea pigs, 79% of the mist trapped in the whole airway was found in the lung, while 49 and 79% of mists produced by DN and UN, respectively, were already deposited in the upper airway. These results strongly suggest that GPN is more useful for inhalation challenge in experimental asthma in animals

Effect of Local Nasal Immunotherapy on Nasal Blockage in Pollen-Induced Allergic Rhinitis of Guinea Pigs

Background: As a non-injection route for immunotherapy, local nasal immunotherapy has been examined in allergic rhinitis patients. However, it is unclear how the immunotherapy affects sneezing, biphasic nasal blockage and nasal hyperresponsiveness. Thus, we evaluated the therapeutic effects of nasal immunotherapy on the symptoms of guinea pig allergic rhinitis. Additionally, we also evaluated whether the immunotherapy relieved pollen-induced allergic conjunctivitis. Methods: Sensitized animals were repeatedly challenged by pollen inhalation once every week. After the 7th challenge, the pollen extract was intranasally administered 6 times a week until the 30th challenge. Sneezing frequency was counted after each of the challenges. As an indicator of nasal blockage, changes in specific airway resistance were measured. Nasal hyperresponsiveness was assessed by measuring leukotriene D4-induced nasal blockage. Additionally, during the immunotherapy, we applied pollen onto the ocular surface to induce the allergic conjunctivitis symptoms. Results: At the 11th—30th challenges, the nasal immunotherapy showed inhibition or a tendency to inhibit the biphasic nasal blockage although the inhibitions were variable at respective challenges. The development of nasal hyperresponsiveness was markedly suppressed by the immunotherapy. Nevertheless, neither sneezing nor antigen-specific IgE antibody production was substantially influenced by the immunotherapy. On the other hand, the nasal immunotherapy did not affect the induction of allergic conjunctivitis symptoms. Conclusions: Local nasal immunotherapy may be clinically useful for allergic nasal blockage associated with nasal hyperresponsiveness. The mechanisms responsible for this effectiveness might not be related to IgE production. Additionally, the effectiveness for nasal tissue was dissociated from that seen for the ocular tissue

Expression of CysLT2 receptors in asthma lung, and their possible role in bronchoconstriction

AbstractBackgroundThe expression and functional role of CysLT2 receptors in asthma have not been clarified. In this study, we evaluated CysLT2 receptors expression, and effects of CysLT2-and CysLT1/2-receptor antagonists on antigen-induced bronchoconstriction using isolated lung tissues from both asthma and non-asthma subjects.MethodsCysLT1 and CysLT2 receptors expression in asthma and non-asthma lung tissue preparations was examined in immunohistochemistry experiments, and their functional roles in antigen-induced bronchoconstriction were assessed using ONO-6950, a dual CysLT1/2-receptor antagonist, montelukast, a CysLT1 receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-specific antagonist.ResultsCysLT1 receptors were expressed on the bronchial smooth muscle and epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2 asthma subjects. On the other hand, although degrees of CysLT2 receptors expression were variable among the 5 non-asthma subjects, the expression in the asthma lung was detected on bronchial smooth muscle, epithelium and alveolar leukocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of CysLT2 receptors did not affect antigen-induced bronchial contractions, even after pretreatment with the CysLT1-receptor specific antagonist, montelukast. However, in the bronchus isolated from one of the 2 asthma subjects, antagonism of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and CysLT2 receptors resulted in additive inhibitory effect on anaphylactic contractions.ConclusionsCysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Activation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population