
Chitinase-Induced Airway Hyperreactivity and Inflammation in a Mouse Model of Nonallergic Asthma
Author(s) -
Christina WeberChrysochoou,
Yasemin Darcan-Nicolaisen,
Johanna Wohlgensinger,
Eva Maria Tinner,
Remo Frei,
Susanne Loeliger,
Roger Lauener,
Eckard Hamelmann
Publication year - 2021
Publication title -
international archives of allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.696
H-Index - 100
eISSN - 1423-0097
pISSN - 1018-2438
DOI - 10.1159/000513296
Subject(s) - chitinase , immunology , zymosan , bronchoalveolar lavage , immune system , chitin , biology , in vitro , medicine , enzyme , lung , biochemistry , chitosan
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. Materials and Methods: 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. Results: 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. Discussion: 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.