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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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- Ekoff, M, et al.
(författare)
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Coaggregation of FcepsilonRI with FcgammaRIIB Inhibits Degranulation but Not Induction of Bcl-2 Family Members A1 and Bim in Mast Cells
- 2006
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Ingår i: Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. - : Springer Science and Business Media LLC. - 1710-1492. ; 2:3, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation of high-affinity immunoglobulin E (IgE) receptors (FcεRI) on mast cells is a critical event in the initiation of an allergic reaction. Coengagement of FcεRI with immunoglobulin G (IgG) low-affinity receptor FcγRIIB/CD32 inhibits degranulation and the release of inflammatory mediators from mast cells and has therefore been proposed as a new therapeutic approach for the treatment of allergies. In this study, we investigated whether FcγRIIB, besides inhibiting degranulation, negatively regulates other signalling pathways downstream of FcεRI. For this, we determined the phosphorylation and/or expression of proteins involved in the regulation of mast-cell apoptosis. Coaggregation led to an attenuation of Akt phosphorylation but did not inhibit phosphorylation of transcription factor Foxo3a or its proapoptotic target, Bim. Similarly, FcεRI-dependent expression of the prosurvival gene A1 was not affected by coaggregation. Our data demonstrate that coengagement of FcεRI and FcγRIIB inhibits degranulation but not the signalling pathways regulating Bcl-2 family members Bim and A1.
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