Inhibition of Airway Inflammation in rDer f 2-Sensitized Mice by Oral Administration of Recombinant Der f 2

Yasue, Masaaki; Yokota, Toyokazu; Kajiwara, Yoshio; Suko, Matsunobu; Okudaira, Hirokazu

doi:10.1006/cimm.1997.1184

Cited by 16 publications

(14 citation statements)

References 42 publications

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“…There are several models of antigen‐specific tolerance that are established in naïve animals before antigen sensitization 12 , 13 , 14 , 15 , 16 , 17 or in sensitized animals prior to the development of AAD 18 , 19 . The phenomenon of LIT differs significantly from the these tolerance models, in that it is established in the presence of AAD and serves to abrogate the allergic inflammatory responses and re‐establish airway homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Subcutaneous late phase responses are augmented during local inhalational tolerance in a murine asthma model

et al. 2008

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Acute exposure of sensitized mice to antigen elicits allergic airway disease (AAD) characterized by Th2 cytokine-dependent pulmonary eosinophilia, methacholine hyperresponsiveness and antigen-specific IgE elevation. However, chronic exposure induces a local inhalational tolerance (LIT), with resolution of the airway responses but persistent systemic IgE production. To further determine if systemic immunologic responses were maintained during LIT, we assessed subcutaneous late phase responses to ovalbumin in this model. Sensitized and AAD mice developed small subcutaneous responses to ovalbumin, with footpad thickness increasing to 113.7 and 113.6% of baseline, respectively. In comparison, LIT mice developed marked foot swelling (141.6%). Histologic examination confirmed increased inflammation in the chronic animals, with a significant contribution by eosinophils. Thus, the resolution of airway inflammatory responses with chronic antigen inhalation is a localized response, not associated with loss of systemic responses to antigen. Keywords: asthma; mouse; ovalbumin; sensitization; tolerance In antigen-sensitized humans and animals, inhalational exposure to the antigen can induce allergic airway disease (AAD), or asthma, characterized by eosinophilic airway inflammation, elaboration of Th2 cytokines and airway hyperresponsiveness. Such individuals also demonstrate systemic responses to antigen, including elevated levels of antigen-specific IgE. Numerous murine models exist in which inhalation of allergens in sensitized mice induces Th2-driven eosinophilic airway disease. We 1,2 and others 3-5 have shown that, in contrast to human subjects, mice exposed chronically to inhaled antigen can reverse their established airway inflammation and hyperresponsiveness, and develop what we have termed local inhalational tolerance (LIT). LIT is dependent upon continuous antigen exposure 2 and is associated with the persistence of CD4 + CD25 + Foxp3 + regulatory T cells in the lung and regional lymph nodes 6 and the establishment of bystander tolerance to unrelated antigens. 2,5 We emphasized the term 'local' because despite resolution of the airway eosinophilia and Th2 cytokine production, systemic IgE responses to antigen are sustained. 2 Although the persistence of the systemic IgE response has also been observed in other chronic inhalational models, 5 it is not a uniform finding in sensitized mice chronically exposed to antigen. 3,4 The maintenance of antigen-specific IgE elevation in the absence of airway inflammatory responses in LIT mice suggests that this form of inhalational tolerance is dependent upon local regulatory mechanisms rather than systemic lymphocyte clonal deletion or anergy. In addition, if chronic aerosolized antigen exposure induces clonal deletion or the development of a dominant, antigen-specific, inhibitory T-cell population, tolerance should be sustained in the absence of antigen or recalled with re-exposure to antigen. We found that such sustained tolerance did not occur in the absence of antigen, as ...

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Section: Resultsmentioning

confidence: 99%

Subcutaneous late phase responses are augmented during local inhalational tolerance in a murine asthma model

et al. 2008

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“…Concerning a mite allergic model, Hsiue et al [4] recently reported the induction of allergic airway inflammation in guinea pigs that showed severe eosinophilia of the airway and immediate bronchoconstriction after intravenous injection of crude mite extract [4]. We have also developed murine allergic models exhibiting immediate airway constriction or neutrophil influx into the airway after antigen inhalation by using rDer f 2 as a sensitizing and provoking antigen [21,22]. However, no reports on the induction of anti-mite IgE in primates have been published to our knowledge.…”

Section: Discussionmentioning

confidence: 99%

Experimental Monkey Model Sensitized with Mite Antigen

Yasue

Nakamura

Yokota

et al. 1998

Int Arch Allergy Immunol

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Background: Monkeys are considered to have an immune system very similar to that of humans, as compared with mice, rats, and guinea pigs. Although primate allergic models to several pollen allergens have been developed, no model of house dust mite allergy has been reported. In this study, we attempted to induce type I allergy to mite allergens in rhesus monkeys. Methods: Six rhesus monkeys were immunized subcutaneously with crude mite extract adsorbed on aluminum hydroxide for 4 months. Then 5 monkeys positive for IgE production to mite extract were further immunized subcutaneously and conjunctivally with recombinant Der f 2 (rDer f 2). The status of sensitization to mite extract and rDer f 2 in monkeys was examined before and after the immunization. Plasma antigen-specific IgE and IgG levels, cutaneous reaction, and histamine release from peripheral blood leukocytes were measured. After conjunctival immunization, immediate conjunctivitis and leukocyte influx into conjunctiva after rDer f 2 challenge were examined. Results: After immunization with crude mite extract, 5 of 6 sensitized monkeys showed IgE response to the mite, and 4 out of 5 rDer f 2-sensitized monkeys exhibited IgE production to rDer f 2. Three monkeys sensitized with rDer f 2 showed immediate conjunctivitis and conjunctival eosinophilia after applying rDer f 2 to their eyes. Sensitized animals also showed IgG response to mite antigens. Conclusion: Four rhesus monkeys were positive for IgE production and allergic reactions to both mite extract and rDer f 2. These monkeys could represent a useful model for studying the development and regulation of house dust mite allergy.

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“…There has been several murine models using Der f 2 but only few researchers evaluated only limited aspects of allergic reactions in mice using rDer f 2 (7,9,10). However, this study shows unique data on the influence of the adjuvants and genetic background on the murine model of asthma using recombinant Der f 2 evaluating the important features of asthma.…”

Section: Resultsmentioning

confidence: 99%

“…Only a few studies used recombinant Der f 2 ( rDer f 2 ) to evaluate its function (4,6-8). Reports on murine asthma model using rDer f 2 are few (9,10). There was no report on the influence of adjuvants and genetic background on the asthma model using rDer f 2 in mice.…”

Section: Introductionmentioning

confidence: 99%

Influence of the Adjuvants and Genetic Background on the Asthma Model Using Recombinant Der f 2 in Mice

et al. 2013

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Der f 2 is the group 2 major allergen of a house dust mite (Dermatophagoides farinae) and its function has been recently suggested. To determine the optimal condition of sensitization to recombinant Der f 2 (rDer f 2) in murine model of asthma, we compared the effectiveness with different adjuvants in BALB/c and C57BL/6 mice. Mice from both strains sensitized with rDer f 2 by intraperitoneal injection or subcutaneous injection on days 1 and 14. The dosage was 20 µg. Freund's adjuvants with pertussis toxin (FP) or alum alone were used as adjuvants. On days 28, 29, and 30, mice were challenged intranasally with 0.1% rDer f 2. We evaluated airway hyperresponsivenss, eosinophil proportion in lung lavage, airway inflammation, and serum allergen specific antibody responses. Naive mice were used as controls. Airway hyperresponsiveness was increased in C57BL/6 with FP, and BALB/c with alum (PC200: 13.5±6.3, 13.2±6.7 vs. >50 mg/ml, p<0.05). The eosinophil proportion was increased in all groups; C57BL/6 with FP, BALB/c with FP, C57BL/6 with alum, BALB/c with alum (24.8±3.6, 20.3±10.3, 11.0±6.9, 5.7±2.8, vs. 0.0±0.0%, p<0.05). The serum allergen specific IgE levels were increased in C57BL/6 with FP or alum (OD: 0.8±1.4, 1.1±0.8, vs. 0.0±0.0). C57BL/6 mice were better responders to rDer f 2 and as for adjuvants, Freund's adjuvant with pertussis toxin was better.

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Inhibition of Airway Inflammation in rDer f 2-Sensitized Mice by Oral Administration of Recombinant Der f 2

Cited by 16 publications

References 42 publications

Subcutaneous late phase responses are augmented during local inhalational tolerance in a murine asthma model

Subcutaneous late phase responses are augmented during local inhalational tolerance in a murine asthma model

Experimental Monkey Model Sensitized with Mite Antigen

Influence of the Adjuvants and Genetic Background on the Asthma Model Using Recombinant Der f 2 in Mice

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