Pollen-derived adenosine is a necessary cofactor for ragweed allergy.
BACKGROUND
Ragweed (Ambrosia artemisiifolia) is a strong elicitor of allergic airway inflammation with worldwide increasing prevalence. Various components of ragweed pollen are thought to play a role in the development of allergic responses. The aim of this study was to identify critical factors for allergenicity of ragweed pollen in a physiological model of allergic airway inflammation.


METHODS
Aqueous ragweed pollen extract, the low molecular weight fraction or the major allergen Amb a 1 was instilled intranasally on 1-11 consecutive days, and allergic airway inflammation was evaluated by bronchoalveolar lavage, lung histology, serology, gene expression in lung tissue, and measurement of lung function. Pollen-derived adenosine was removed from the extract enzymatically to analyze its role in ragweed-induced allergy. Migration of human neutrophils and eosinophils toward supernatants of ragweed-stimulated bronchial epithelial cells was analyzed.


RESULTS
Instillation of ragweed pollen extract, but not of the major allergen or the low molecular weight fraction, induced specific IgG1 , pulmonary infiltration with inflammatory cells, a Th2-associated cytokine signature in pulmonary tissue, and impaired lung function. Adenosine aggravated ragweed-induced allergic lung inflammation. In vitro, human neutrophils and eosinophils migrated toward supernatants of bronchial epithelial cells stimulated with ragweed extract only if adenosine was present.


CONCLUSIONS
Pollen-derived adenosine is a critical factor in ragweed-pollen-induced allergic airway inflammation. Future studies aim at therapeutic strategies to control these allergen-independent pathways.
Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.|Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.
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Wimmer
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.
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Alessandrini
Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.
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Gilles
Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.|Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, Munich, Germany.
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Frank
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.
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Oeder
Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.|Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
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Hauser
Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.|Department of Dermatology and Allergy Biederstein, TU Munich, Munich, Germany.
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Ring
Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
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Ferreira
Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, Munich, Germany.
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Ernst
Research Unit Environmental Simulation at the Institute of Biochemical Plant Pathology, Helmholtz Zentrum München, Munich, Germany.
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Winkler
Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Munich, Germany.|Analytical Food Chemistry, Technische Universität München, Munich, Germany.
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Schmitt-Kopplin
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.
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Ohnmacht
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.
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Behrendt
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.
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Schmidt-Weber
Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, Zurich, Switzerland.|Department of Dermatology and Allergy Biederstein, TU Munich, Munich, Germany.
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Traidl-Hoffmann
Center of Allergy and Environment (ZAUM), Technische Universität and Helmholtz Zentrum München, Member of the German Center for Lung research (DZL), Munich, Germany.|Department of Dermatology and Allergy Biederstein, TU Munich, Munich, Germany.|Department of Dermatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussel, Belgium.
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Gutermuth
D000241:Adenosine / Q000378:metabolism*; D000281:Administration, Intranasal; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000276:immunology*; D011897:Random Allocation; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D052179:Antigens, Plant; D010936:Plant Extracts; C433085:ragweed pollen; D000241:Adenosine
adenosine; adjuvant; allergic inflammation; ragweed; sensitization