Pollen-derived adenosine is a necessary cofactor for ragweed allergy

Allergy. 2015 Aug;70(8):944-54. doi: 10.1111/all.12642. Epub 2015 May 28.

Abstract

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.

Keywords: adenosine; adjuvant; allergic inflammation; ragweed; sensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism*
  • Administration, Intranasal
  • Animals
  • Antigens, Plant / immunology*
  • Asthma / immunology
  • Asthma / physiopathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Immunization / methods*
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Plant Extracts / immunology*
  • Random Allocation
  • Respiratory Hypersensitivity / physiopathology*
  • Risk Assessment
  • Sensitivity and Specificity
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Antigens, Plant
  • Plant Extracts
  • ragweed pollen
  • Adenosine