Effect of adenosine receptors stimulation on generation of CD1a low CD14 ⁺ CD209 ⁺ cells in patients with bronchial asthma

Background: Increased concentration of adenosine have been found in bronchoalveolar lavage, blood and exhaled breath condensate of patients with BA (Spicuzza et al , Eur J Pharmacol. 2006;533:77-88). Adenosine skews dendritic cell (DC's) differentiation toward cell population characterized by CD1a low CD14 + CD209 + antigenic phenotype and high expression of proinflammatory cytokines (Novitskiy et al , Blood 2008;112:1822-31). Aim: To investigate effects of adenosine receptors (AdoR's) stimulation during initial time period of DC's differentiation from peripheral blood (PB) monocytes in patients with bronchial asthma. Methods: PB monocytes were received from 32 subjects diagnosed with BA and 19 healthy volunteers and cultured in DC-differentiation medium in the absence or presence of AdoR's agonist NECA (30μM) for 38 hours. Cell surface expression of CD1a, CD14 and CD209 was analyzed by FACS. Results: We have found that stimulation of AdoR's results in higher yield of CD1a low CD14 + CD209 + cells in patients with BA compare to healthy volunteers (8.22% ±1.72% and 3.43%±0.83%, in BA patients and healthy volunteers respectively; p<0,05). According to number of CD1a low CD14 + CD209 + cells generated after treatment with NECA we documented the presence of two groups of individuals characterized by high and low response to AdoR's stimulation. We identified that 50% of individuals with BA and 16% of healthy volunteers demonstrated high responsiveness to NECA. Conclusion: Our study indicates the role of adenosine regulation of DC's differentiation in BA. The heterogeneity in responses to AdoR's stimulation may be used as a basis for individual BA treatment development.