Allergy Unit, Dermatology Department, University Hospital of Zurich, Zurich, Switzerland,
Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany.
Int Arch Allergy Immunol. 2021;182(7):563-570. doi: 10.1159/000513296. Epub 2021 Mar 17.
Environmental exposure to mites and fungi has been proposed to critically contribute to the development of IgE-mediated asthma. A common denominator of such organisms is chitin. Human chitinases have been reported to be upregulated by interleukin-13 secreted in the context of Th2-type immune responses and to induce asthma. We assessed whether chitin-containing components induced chitinases in an innate immune-dependent way and whether this results in bronchial hyperresponsiveness.
Monocyte/macrophage cell lines were stimulated with chitin-containing or bacterial components in vitro. Chitinase activity in the supernatant and the expression of the chitotriosidase gene were measured by enzyme assay and quantitative PCR, respectively. Non-sensitized mice were stimulated with chitin-containing components intranasally, and a chitinase inhibitor was administered intraperitoneally. As markers for inflammation leukocytes were counted in the bronchoalveolar lavage (BAL) fluid, and airway hyperresponsiveness was assessed via methacholine challenge.
We found both whole chitin-containing dust mites as well as the fungal cell wall component zymosan A but not endotoxin-induced chitinase activity and chitotriosidase gene expression in vitro. The intranasal application of zymosan A into mice led to the induction of chitinase activity in the BAL fluid and to bronchial hyperresponsiveness, which could be reduced by applying the chitinase inhibitor allosamidin.
We propose that environmental exposure to mites and fungi leads to the induction of chitinase, which in turn favors the development of bronchial hyperreactivity in an IgE-independent manner.
环境中螨和真菌的暴露被认为对 IgE 介导的哮喘的发展有重要影响。这些生物体的一个共同点是几丁质。据报道，白细胞介素-13 在 Th2 型免疫反应中分泌，可上调人类几丁质酶，并诱发哮喘。我们评估了几丁质含有的成分是否以先天免疫依赖的方式诱导几丁质酶，以及这是否导致支气管高反应性。
体外用含几丁质或细菌成分的单核细胞/巨噬细胞系进行刺激。通过酶谱法和定量 PCR 分别测定上清液中的几丁质酶活性和几丁质酶基因的表达。用含几丁质的成分对未致敏的小鼠进行鼻内刺激，并腹腔内给予几丁质酶抑制剂。通过乙酰甲胆碱挑战来评估气道高反应性，同时对支气管肺泡灌洗液（BAL）中的白细胞计数作为炎症标志物。
我们发现，整个含几丁质的尘螨以及真菌细胞壁成分 zymosan A 但不是内毒素都能诱导体外的几丁质酶活性和几丁质酶基因表达。将 zymosan A 鼻内应用于小鼠，导致 BAL 液中几丁质酶活性的诱导和支气管高反应性，而应用几丁质酶抑制剂 allo samidin 可降低这种反应。
我们提出，环境中螨和真菌的暴露导致几丁质酶的诱导，而几丁质酶反过来又以 IgE 非依赖的方式有利于支气管高反应性的发展。
