Oxidative/nitrosative stress selectively altered A2B adenosine receptors in chronic obstructive pulmonary disease.

The primary aim of this study was to
investigate adenosine receptors (ARs) in bronchoalveolar
lavage (BAL) macrophages from patients with
chronic obstructive pulmonary disease (COPD) and
age-matched healthy smokers. A2BARs were significantly
decreased in BAL macrophages from patients
with COPD when compared with healthy smokers. The
effect of proinflammatory cytokines and oxidative/
nitrosative stress on AR expression and function in
U937 cells before and after PMA treatment was evaluated.
IL-1 and TNF- treatment up-regulated A2A- and
A3ARs but not A1- or A2BARs, whereas IL-6 did not
modify AR expression. In contrast, oxidative/nitrosative
stress selectively decreased A2BAR expression,
which was associated with a reduction in the potency of
the adenosine agonist 5-N-ethylcarboxamideadenosine
(NECA) to induce cAMP. Further, the ability of NECA
to enhance cell proliferation was increased after oxidative/
nitrosative stress. The specific involvement of
A2BARs was investigated by using potent and selective
A2BAR antagonist and by A2BAR knockdown using
siRNA and demonstrated responses similar to those
obtained with oxidative/nitrosative stress. N-acetylcysteine
(NAC), an antioxidant agent, counteracted the
decrease in A2BAR expression, as well as the altered
NECA effects on cAMP and cell proliferation. These
findings highlight the central role of A2BARs in alveolar
macrophages, suggesting that their modulation could
represent an innovative pharmacological strategy to
manage COPD.—Varani, K., Caramori, G., Vincenzi,
F., Tosi, A., Barczyk, A., Contoli, M., Casolari, P.,
Triggiani, M., Hansel, T., Leung, E., MacLennan, S.,
Barnes, P. J., Fan Chung, K., Adcock, I., Papi, A.,
Borea, P. A. Oxidative/nitrosative stress selectively
altered A2B adenosine receptors in chronic obstructive
pulmonary disease.