Christina Weber-Chrysochoou1, Yasemin Darcan-Nicolaisen2, Johanna Wohlgensinger3,4, Eva Maria Tinner5,6, Remo Frei4,7, Susanne Loeliger3,4, Roger P Lauener4,8, Eckard Hamelmann2,9. 1. Allergy Unit, Dermatology Department, University Hospital of Zurich, Zurich, Switzerland, christina.weber@usz.ch. 2. Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany. 3. University Children's Hospital Zurich, Zurich, Switzerland. 4. Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland. 5. Division of Pediatric Hematology/Oncology, University Children's Hospital of Bern, Inselspital, Bern, Switzerland. 6. Department of Medicine, Kantonsspital Baselland, Liestal, Switzerland. 7. Division of Respiratory Medicine, Department of Pediatrics, University of Bern Inselspital, Bern, Switzerland. 8. Children's Hospital St Gallen, St Gallen, Switzerland. 9. Department of Pediatrics, Evangelisches Klinikum Bethel EvKB, University Bielefeld, Bielefeld, Germany.
Abstract
INTRODUCTION: 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.
INTRODUCTION: 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.
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