Allergen inhalation decreases adenosine receptor expression in sputum and blood of asthma patients

• Published in: Allergy (Copenhagen) 2008-09, Vol.63 (9), p.1186-1194
• Main Authors: Versluis, M, van den Berge, M, Timens, W, Luijk, B, Rutgers, B, Lammers, J.-W.J, Postma, D.S, Hylkema, M.N
• Format: Article
• Language: English
• Subjects: adenosine; adenosine receptors; Adult; allergen challenge; Allergens; Asthma; Asthma - blood; Asthma - genetics; Biological and medical sciences; Blood; Body fluids; Bronchial Provocation Tests; Cellular biology; Cytokines; Dermatology; Down-Regulation; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Humans; Immune system; Male; Medical sciences; Middle Aged; Receptor, Adenosine A1 - metabolism; Receptor, Adenosine A2A - metabolism; Receptor, Adenosine A2B - metabolism; Receptors, Purinergic P1 - blood; Receptors, Purinergic P1 - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Sputum - metabolism; thymic stromal lymphopoietin
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2008.01735.x

Adenosine is a signalling nucleoside that has been proposed to contribute to the pathogenesis of asthma. Adenosine is produced in inflammatory environments and acts via adenosine receptors (A₁R, A₂AR, A₂BR, and A₃R) expressed by a wide variety of cells, resulting in pro- and anti-inflammatory effects. To compare AR expression in asthma patients and healthy subjects, and to assess the effect of allergen challenge on AR expression of inflammatory cells and on cytokines in peripheral blood and sputum in asthma. Asthma patients underwent an allergen challenge, and blood and induced sputum samples were taken before and 24 h after allergen challenge to study inflammatory cells numbers, AR expression and cytokine production. Blood and sputum were investigated at one time point in healthy subjects. AR expression was measured by flow cytometry (blood) or on cytospins using immunocytochemistry (sputum). Cytokines (luminex, ELISA) and adenosine (HPLC) were measured in sputum supernatant. The percentage of A₂BR expressing neutrophils in sputum was lower in asthma patients than in healthy subjects (P = 0.016). Allergen challenge decreased A₁R and A₂AR expression on neutrophils and A₁R expression on T cells in peripheral blood (all P < 0.05). Allergen challenge increased IL-8 levels and eosinophil numbers (P < 0.05), whereas it decreased thymic stromal lymphopoietin levels and the percentage of A₁R expressing macrophages in induced sputum (P < 0.05). Allergen challenge has a down-regulatory effect on AR expression in asthma, suggesting a contribution of adenosine-related effector mechanisms in the pathophysiology.