Purinergic regulation of airway inflammation

The immune and inflammatory responses initiated by the interaction of a pathogen with airway surfaces constitute vital mechanisms to eradicate an infection. Sentinel dendritic cells embedded in the mucosa migrate to the lymph nodes to induce immune responses, whereas epithelial cells release chemokines to recruit inflammatory cells engaged in the active destruction of the intruder. All immune and inflammatory cells are regulated by customized purinergic networks of receptors and ectonucleotidases. The general concept is that bacterial products induce ATP release, which activates P2 receptors to initiate an inflammatory response, and is terminated by the conversion of ATP into adenosine (ADO) to initiate P1 receptor-mediated negative feedback responses. However, this chapter exposes a far more complex purinergic regulation of critical functions, such as the differentiation of naive lymphocytes and the complex maturation and secretion of pro-cytokines (i.e. IL-1β) by the "inflammasome". This material also reconciles decades of research by exposing the specificity and plasticity of the signaling network expressed by each immune and inflammatory cell, which changes through cell differentiation and in response to infectious or inflammatory mediators. By the end of this chapter, the reader will have a new appreciation for this aspect of airway defenses, and several leads in terms of therapeutic applications for the treatment of chronic respiratory diseases.