Levels of purines are increased in airways of patients with asthma or chronic obstructive pulmonary disease (COPD). Adenosine is formed by dephosphorylation of AMP by ecto-5´-nucleotidase (CD73). A previous report showed that bleomycin treated CD73-/- mice exhibit enhanced pulmonary inflammation and fibrosis. We investigated the effects of purines on tracheal electrolyte transport in an allergic mouse model. Balbc and CD73-/- mice were sensitised with chicken egg ovalbumin (OVA) and challenged with OVA. In OVA challenged Balbc mice the effects of ATP, ADP, AMP and adenosine (each 100 mM) on Cl - secretion were increased. RT-PCR showed elevated expression of P2Y6 and A2B receptors. In CD73-/- mice AMP was not able to induce Cl- secretion, indicating lack of AMP degradation to adenosine missing CD73. ATP and ADP increased Cl- secretion in OVA treated CD73+/+ mice. However in trachea of OVA challanged CD73-/- mice there was no increased sensitivity towards ATP and ADP. These results suggest that enhanced pulmonary inflammation in CD73-/- mice may be due to reduced ability of purines to induce Cl- secretion and therefore impaired mucus clearance.

This study is supported by Else Kröner- Fresenius- Stiftung and SFB 699 A7.