Purinergic signalling in the lung: involvement in the pathogenesis of asthma and COPD

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The pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) is not fully understood yet. Endogenous released nucleotides (like ATP, ADP, UTP, UDP) have recently gained attention as a mediator of intercellular communication via the activation of purinergic receptors (P2XR and P2YR). While the role of adenosine (a metabolite of ATP/ADP) in the pathogenesis of asthma and COPD has been extensively studied, little is know about P2R-mediated immune-responses in airway inflammation. Recently we could show that ATP release into the airways during acute asthma, favours Th2 development by altering the function of lung DC. In addition neutralization of endogenous airway ATP or unselective blocking of P2R abrogates the cardinal features of asthma. Therefore, goal of the present project is: 1) to identify the precise P2R involved in mediating the typical features of acute; 2) to determine the role of P2R signalling in chronic asthma 3) to evaluate the clinical relevance by using hu-SCID mouse model of asthma (reconstituted with blood from asthmatic patients; 4) to measure nucleotides levels in bronchoalveolar lavage of asthmatic and COPD patients; 5) to ascertain the role of P2 signalling in COPD by neutralizing airway nucleotides levels and blocking of P2R in mouse model of COPD. These studies will provide important information on P2R signalling involved in the pathogenesis of asthma and COPD, and could lead to the discovery of a whole new therapeutic class of drugs to control chronic airway inflammation.