In:
Allergy, Wiley, Vol. 75, No. 3 ( 2020-03), p. 603-615
Abstract:
Allergic diseases and especially allergic asthma are widespread diseases with high prevalence in childhood, but also in adults. Acid sphingomyelinase (ASM) is a key regulator of the sphingolipid pathway. Previous studies defined the association of ASM with the pathogenesis of T H 1‐directed lung diseases like cystic fibrosis and acute lung injury. Here, we define the role of ASM in T H 2‐regulated allergic bronchial asthma. Methods To determine the role of Asm under baseline conditions, wild‐type (WT) and Asm −/− mice were ventilated with a flexiVent setup and bronchial hyperresponsiveness was determined using acetylcholine. Flow cytometry and cytokine measurements in bronchoalveolar lavage fluid and lung tissue were followed by in vitro T H 2 differentiations with cells from WT and Asm −/− mice and blockade of Asm with amitriptyline. As proof of principle, we conducted an ovalbumin‐induced model of asthma in WT‐ and Asm −/− mice. Results At baseline, Asm −/− mice showed better lung mechanics, but unaltered bronchial hyperresponsiveness. Higher numbers of Asm −/− T cells in bronchoalveolar lavage fluid released lower levels of IL‐4 and IL‐5, and these results were paralleled by decreased production of typical T H 2 cytokines in Asm −/− T lymphocytes in vitro. This phenotype could be imitated by incubation of T cells with amitriptyline. In the ovalbumin asthma model, Asm −/− animals were protected from high disease activity and showed better lung functions and lower levels of eosinophils and T H 2 cytokines. Conclusion Asm deficiency could induce higher numbers of T H 2 cells in the lung, but those cells release decreased T H 2 cytokine levels. Hereby, Asm −/− animals are protected from bronchial asthma, which possibly offers novel therapeutic strategies, for example, with ASM blockade.
Type of Medium:
Online Resource
ISSN:
0105-4538
,
1398-9995
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2003114-2
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