Intratracheal Sensitization/Challenge-Induced Biphasic Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

Mizutani, Nobuaki; Inui, Shouichi; Yoshino, Shigefumi; Nabe, Takeshi

doi:10.1248/bpb.33.1949

Cited by 6 publications

(2 citation statements)

References 21 publications

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“…We first successfully established the animal model of airway allergic inflammation. Consistent with previous reports, [33][34][35] our findings in vivo suggested that OVA challenge resulted in a significant increase of the OVAspecific Th2 subset, elevation of OVA-sIgE levels, and intensive eosinophil infiltration in the airway walls, which mimics the typical symptoms of human allergic airway inflammation. We then investigated the changes in basophil number and activity following OVA challenge.…”

Section: Discussionsupporting

confidence: 92%

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

Zhong

Zhang

et al. 2014

Immunology

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SummaryAntigen-induced allergic airway inflammation is mediated by T helper type 2 (Th2) cells and their cytokines, but the mechanism that initiates the Th2 immunity is not fully understood. Recent studies show that basophils play important roles in initiating Th2 immunity in some inflammatory models. Here we explored the role of basophils in ovalbumin (OVA) -induced airway allergic inflammation in BALB/c mice. We found that OVA sensitization and challenge resulted in a significant increase in the amount of basophils in blood and lung, along with the up-regulation of activation marker of CD200R. However, depletion of basophils with MAR-1 or Ba103 antibody attenuated airway inflammation, represented by the significantly decreased amount of the Th2 subset in spleen and draining lymph nodes, interlukin-4 level in lung and OVA-special immunoglobulin E (sIgE) levels in serum. On the other hand, adoptive transfer of basophils from OVA-challenged lung tissue to naive BALB/c mice provoked the Th2 immune response. In addition, pulmonary basophils from OVA-challenged mice were able to uptake DQ-OVA and express MHC class II molecules and CD40 in vivo, as well as to release interleukin-4 following stimulation by IgE-antigen complexes and promote Th2 polarization in vitro. These findings demonstrate that basophils may participate in Th2 immune responses in antigen-induced allergic airway inflammation and that they do so through facilitating antigen presentation and providing interleukin-4.

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Section: Discussionsupporting

confidence: 92%

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

Zhong

Zhang

et al. 2014

Immunology

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“…Previous studies have utilized single-or double-chambered plethysmographs to show allergen-induced responses in the guinea-pig [28][29][30][31]. In this study, we used the forced-oscillation technique to demonstrate a prominent increase in lung resistance during EAR [32].…”

Section: Discussionmentioning

confidence: 99%

Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma

et al. 2013

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One feature of allergic asthma, the EAR (early allergic reaction), is not present in the commonly used mouse models. We therefore investigated the mediators involved in EAR in a guinea-pig in vivo model of allergic airway inflammation. Animals were sensitized using a single OVA (ovalbumin)/alum injection and challenged with aerosolized OVA on day 14. On day 15, airway resistance was assessed after challenge with OVA or MCh (methacholine) using the forced oscillation technique, and lung tissue was prepared for histology. The contribution of mast cell mediators was investigated using inhibitors of the main mast cell mediators [histamine (pyrilamine) and CysLTs (cysteinyl-leukotrienes) (montelukast) and prostanoids (indomethacin)]. OVA-sensitized and challenged animals demonstrated AHR (airway hyper-responsiveness) to MCh, and lung tissue eosinophilic inflammation. Antigen challenge induced a strong EAR in the sensitized animals. Treatment with a single compound, or indomethacin together with pyrilamine or montelukast, did not reduce the antigen-induced airway resistance. In contrast, dual treatment with pyrilamine together with montelukast, or triple inhibitor treatment, attenuated approximately 70% of the EAR. We conclude that, as in humans, the guinea-pig allergic inflammation model exhibits both EAR and AHR, supporting its suitability for in vivo identification of mast cell mediators that contribute to the development of asthma. Moreover, the known mast cell mediators histamine and leukotrienes were major contributors of the EAR. The data also lend further support to the concept that combination therapy with selective inhibitors of key mediators could improve asthma management.

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Pathogenesis of Infection with 2009 Pandemic H1N1 Influenza Virus in Isogenic Guinea Pigs after Intranasal or Intratracheal Inoculation

Wiersma

Trierum

Amerongen

et al. 2015

The American Journal of Pathology

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To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission.

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Intratracheal Sensitization/Challenge-Induced Biphasic Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

Cited by 6 publications

References 21 publications

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

Basophils as a primary inducer of the T helper type 2 immunity in ovalbumin‐induced allergic airway inflammation

Mast cell mediators cause early allergic bronchoconstriction in guinea-pigs in vivo: a model of relevance to asthma

Pathogenesis of Infection with 2009 Pandemic H1N1 Influenza Virus in Isogenic Guinea Pigs after Intranasal or Intratracheal Inoculation

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