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- Fuchs, B, et al.
(författare)
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Mast cell engraftment of the peripheral lung enhances airway hyperresponsiveness in a mouse asthma model
- 2012
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Ingår i: American journal of physiology. Lung cellular and molecular physiology. - : American Physiological Society. - 1522-1504 .- 1040-0605. ; 303:12, s. L1027-L1036
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Tidskriftsartikel (refereegranskat)abstract
- Allergic asthma is a chronic inflammatory disease, characterized by airway hyperresponsiveness (AHR), inflammation, and tissue remodeling, in which mast cells play a central role. In the present study, we analyzed how mast cell numbers and localization influence the AHR in a chronic murine model of asthma. C57BL/6 (wild-type) and mast cell-deficient B6.Cg- KitW−shmice without (Wsh) and with (Wsh+MC) mast cell engraftment were sensitized to and subsequently challenged with ovalbumin for a 91-day period. In wild-type mice, pulmonary mast cells were localized in the submucosa of the central airways, whereas the more abundant mast cells in Wsh+MC mice were found mainly in the alveolar parenchyma. In Wsh+MC, ovalbumin challenge induced a relocation of mast cells from the perivascular space and central airways to the parenchyma. Allergen challenge caused a similar AHR in wild-type and Wsh mice in the resistance of the airways and the pulmonary tissue. In Wsh+MC mice the AHR was more pronounced. The elevated functional responses were partly related to the numbers and localization of connective tissue-type mast cells in the peripheral pulmonary compartments. A mast cell-dependent increase in IgE and IL-33 together with impairment of the IL-23/IL-17 axis was evoked in Wsh and Wsh+MC mice by allergen challenge. This study shows that within the same chronic murine asthma model the development of AHR can be both dependent and independent of mast cells. Moreover, the spatial distribution and number of pulmonary mast cells determine severity and localization of the AHR.
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- Neimert-Andersson, T., et al.
(författare)
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Carbohydrate-based particles reduce allergic inflammation in a mouse model for cat allergy
- 2008
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 63:5, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergen-specific immunotherapy (ASIT) is the only treatment of allergic disease that gives long-lasting relief of symptoms. However, concerns for safety and efficiency have highlighted the need for improvement of the therapy. We have previously suggested carbohydrate-based particles (CBPs) as a novel adjuvant and allergen carrier for ASIT. Our aim of this study was to evaluate the therapeutic potential of CBPs in ASIT, employing a mouse model for cat allergy. Methods: BALB/c mice were subcutaneously immunized with the recombinant (r) cat allergen Fel d 1 followed by intranasal challenge with cat dander extract (CDE). The sensitized mice were therapeutically treated with rFel d 1 covalently coupled to CBPs (CBP-rFel d 1). Airway hyper-reactivity (AHR), infiltration of leucocytes in bronchoalveolar lavage (BAL) fluid, allergen-specific serum immunoglobulin levels and in vitro splenocyte responses were evaluated. Results: Mice treated with CBP-rFel d 1 showed reduced features of allergic inflammation. They responded with (i) significantly decreased AHR and infiltration of eosinophils in BAL fluid after CDE challenge, (ii) the serum level of rFel d 1-specific IgE was reduced and the level of IgG(2)a was more pronounced after CBP-rFel d 1 treatment, and (iii) there was also a tendency of decreased allergen-specific cellular response. Conclusions: Carbohydrate-based particles are effective tools as adjuvant and allergen carriers for use in ASIT and constitutes a promising strategy to improve allergy treatment.
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