Extracellular ATP and related nucleotides promote a wide range of pathophysiological responses via activation of cell surface purinergic P2 receptors. Almost every cell type expresses P2 receptors and/or exhibit regulated release of ATP. In this review, we focus on the purinergic receptor distribution in inflammatory cells and their implication in diverse immune responses by providing an overview of the current knowledge in the literature related to purinergic signaling in neutrophils, macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells. The pathophysiological role of purinergic signaling in these cells include among others calcium mobilization, actin polymerization, chemotaxis, release of mediators, cell maturation, cytotoxicity, and cell death. We finally discuss the therapeutic potential of P2 receptor subtype selective drugs in inflammatory conditions.

Inflammation of the nasal (rhinitis) and sinus mucosa (sinusitis) are prevalent medical conditions of the upper airways that are concurrent in many patients; hence the terminology "rhinosinusitis". The disease status is further defined to be "chronic" in case symptoms persist for more than 12 weeks without resolution. A diverse spectrum of external factors including viral and bacterial insults together with epithelial barrier malfunctions could be implicated in the chronicity of the inflammatory responses in chronic rhinosinusitis (CRS). However, despite massive research efforts in an attempt to unveil the pathophysiology, the exact reason for a lack of resolution still remains poorly understood. A novel set of molecules that could be implicated in sustaining the inflammatory reaction may be found within the host itself. Indeed, besides mediators of inflammation originating from outside, some endogenous intracellular and/or extracellular matrix (ECM) components from the host can be released into the extracellular space upon damage induced during the initial inflammatory reaction where they gain functions distinct from those during normal physiology. These "host-self" molecules are known to modulate inflammatory responses under pathological conditions, potentially preventing resolution and contributing to the development of chronic inflammation. These molecules are collectively classified as damage-associated molecular patterns (DAMPs). This review summarizes the current knowledge regarding DAMPs in upper airway pathologies, also covering those that were previously investigated for their intracellular and/or ECM functions often acting as an antimicrobial agent or implicated in tissue/cell homeostasis, and for which their function as a danger signaling molecule was not assessed. It is, however, of importance to assess these molecules again from a point of view as a DAMP in order to further unravel the pathogenesis of CRS.