Repeated Antigen Inhalation-Induced Reproducible Early and Late Asthma in Guinea Pigs.

Nabe, Takeshi; Shinoda, Naoki; Yamada, Masahiro; Sekioka, Tomohiko; Saeki, Yuji; Yamamura, Hideki; Kohno, Shigekatsu

doi:10.1254/jjp.75.65

Cited by 24 publications

(24 citation statements)

References 27 publications

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“…Our previous animal model of asthma was developed by exposing guinea pigs to a fine mist of antigen solution. 13) However, it took more than 4 months to induce an LAR. Another key finding of the current study is that the EAR, LAR, and airway hyperresponsiveness were induced by the first antigen challenge, and took only 19 d, although only the EAR was induced after the first challenge in our previous model.…”

Section: Discussionmentioning

confidence: 99%

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

Mizutani

Inui²,

Yoshino

et al. 2010

Biological & Pharmaceutical Bulletin

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In most experimental model of asthma using guinea pigs, the animals are made to inhale an aerosolized antigen which passes through the nasal cavity. In the present study, we attempted to create an animal model of asthma showing a biphasic asthmatic response and airway hyperresponsiveness, in which the allergic responses are restricted to the lung. Guinea pigs were sensitized by the intratracheal instillation of ovalbumin (OVA)؉Al(OH) 3 once a day for 7 d, and then intratracheally challenged with OVA 12 d after the last sensitization. The change in specific airway resistance (sRaw) and airway responsiveness to histamine were measured. Pranlukast (100 mg/kg), theophylline (50 mg/kg), and dexamethasone (10 mg/kg) were orally administered 18 and 2 h before the antigen challenge. The challenge caused a marked biphasic elevation of sRaw with peaks at 5 min and 4 h. At 24 h, airway hyperresponsiveness to histamine was observed. Pranlukast, theophylline, and dexamethasone suppressed the late asthmatic response and airway hyperresponsiveness. The early asthmatic response was inhibited by theophylline and dexamethasone. In conclusion, the intratracheal sensitization and challenge caused a biphasic asthmatic response and airway hyperresponsiveness in guinea pigs. This model may be useful for the evaluation of anti-asthma drugs.

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Section: Discussionmentioning

confidence: 99%

“…However, approximately 20% of the mist trapped in the airway tissues was found to be deposited in the nasal mucosa despite using the glassware pressure nebulizer. 14) In addition, it took more than 4 months to induce the LAR through repeated the aerosols, 13) not particularly convenient for pharmacological examinations of anti-asthma drugs.…”

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confidence: 99%

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

Mizutani

Inui²,

Yoshino

et al. 2010

Biological & Pharmaceutical Bulletin

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“…injection with ovalbumin (OVA; 50 mg, Grade V; Sigma-Aldrich, St. Louis, MO, USA) adsorbed to alum (2 mg in 0.5 mL PBS) on days 0, 14 and 28. The alum was prepared as previously described (Nabe et al, 1997). Sensitized mice were challenged on days 35, 36, 37 and 40 under inhalation anaesthesia using isoflurane (Dainippon Pharmaceutical Co., Osaka, Japan) with 2% OVA administered i.t.…”

Section: Sensitization and Challengementioning

confidence: 99%

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Nabe

Matsuya

Akamizu

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEMast cell hyperplasia has been observed in the lungs of mice with experimental asthma, but few reports have studied basophils. Here, we attempted to discriminate and quantify mast cells and basophils in the lungs in a murine asthma model, determine if both cells were increased by multiple antigen challenges and assess the roles of those cells in asthmatic responses. EXPERIMENTAL APPROACHSensitized Balb/c mice were intratracheally challenged with ovalbumin four times. Mast cells and basophils in enzymatically digested lung tissue were detected by flow cytometry. An anti-FceRI monoclonal antibody, MAR-1, was i.p. administered during the multiple challenges. KEY RESULTSThe numbers of both mast cells (IgE + C-kit + ) and basophils (IgE + C-kit -CD49b + ) increased in the lungs after three challenges. Treatment with MAR-1 completely abolished the increases; however, a late-phase increase in specific airway resistance (sRaw), and airway eosinophilia and neutrophilia were not affected by the treatment, although the early-phase increase in sRaw was suppressed. MAR-1 reduced antigen-induced airway IL-4 production. Basophils infiltrating the lung clearly produced IL-4 after antigen stimulation in vitro; however, histamine and murine mast cell protease 1 were not increased in the serum after the challenge, indicating that mast cell activation was not evoked. CONCLUSION AND IMPLICATIONSBoth mast cells and basophils infiltrated the lungs by multiple intratracheal antigen challenges in sensitized mice. Neither mast cells nor basophils were involved in late-phase airway obstruction, although early-phase obstruction was mediated by basophils. Targeting basophils in asthma therapy may be useful for an early asthmatic response.

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“…However, only the early bronchoconstrictive response was induced by OA inhalation in guinea pigs sensitized passively with anti-OA antiserum. Results of other studies (10,12,13), including our previous report (14), have also indicated that repeated antigen inhalation causes a biphasic asthmatic response. In contrast to the situation with lower airway obstructive responses, research on experimental models of allergic rhinitis has not been very extensive.…”

Section: Resultsmentioning

confidence: 64%

Comparison of Cedar Pollen-Induced Allergic Rhinitis in Passively and Actively Sensitized Guinea Pigs

Nabe

Mizutani

Osaki

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H 1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.

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Repeated Antigen Inhalation-Induced Reproducible Early and Late Asthma in Guinea Pigs.

Cited by 24 publications

References 27 publications

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

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

Roles of basophils and mast cells infiltrating the lung by multiple antigen challenges in asthmatic responses of mice

Comparison of Cedar Pollen-Induced Allergic Rhinitis in Passively and Actively Sensitized Guinea Pigs

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