Allergen inhalation decreases adenosine receptor expression in sputum and blood of asthma patients.
BACKGROUND
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 (A(1)R, A(2A)R, A(2B)R, and A(3)R) expressed by a wide variety of cells, resulting in pro- and anti-inflammatory effects.


OBJECTIVE
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.


METHODS
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.


RESULTS
The percentage of A(2B)R expressing neutrophils in sputum was lower in asthma patients than in healthy subjects (P = 0.016). Allergen challenge decreased A(1)R and A(2A)R expression on neutrophils and A(1)R 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 A(1)R expressing macrophages in induced sputum (P < 0.05).


CONCLUSIONS
Allergen challenge has a down-regulatory effect on AR expression in asthma, suggesting a contribution of adenosine-related effector mechanisms in the pathophysiology.
Versluis
M
M
Department of Pathology and Laboratory Medicine, University Medical Centrer Groningen, University of Groningen, Groningen, the Netherlands.
van den Berge
M
M
Timens
W
W
Luijk
B
B
Rutgers
B
B
Lammers
J-W J
JW
Postma
D S
DS
Hylkema
M N
MN
D000328:Adult; D000485:Allergens; D001249:Asthma / Q000097:blood* / Q000235:genetics; D001985:Bronchial Provocation Tests; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000097:blood / Q000378:metabolism*; D013183:Sputum / Q000378:metabolism*
D000485:Allergens; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D018047:Receptors, Purinergic P1