Bours Martijn Jan Leo, Dagnelie Pieter Cornelis, Giuliani Anna Lisa, Wesselius Anke, Di Virgilio Francesco
Maastricht University, Department of Epidemiology, School for Public Health and Primary Care (CAPHRI), Maastricht, The Netherlands.
Front Biosci (Schol Ed). 2011 Jun 1;3(4):1443-56. doi: 10.2741/235.
Inflammation is an important homeostatic response, which is managed by a complex network of interrelated pathways that determine the level, intensity and localization of inflammation. We now know that purinergic signalling is one of the pathways influencing the initiation, progression and down-modulation of the inflammatory response. Here, we review recent evidence on the role in inflammation of the purinergic signalling system, which is comprised of extracellular ATP, P2 receptors and ecto-enzyme cascades. Recent animal studies with a newly developed bioluminescent ATP probe (pmeLUC), enabling measurement of pericellular ATP in situ, have provided proof that ATP is present in inflamed tissues in vivo at extracellular concentrations sufficient for P2 receptor activation. Increased extracellular ATP levels amplify inflammation in vivo by promoting leukocyte recruitment and NALP3-inflammasome activation via P2X7. Lowering extracellular ATP levels in inflamed tissues, for instance by stimulating its breakdown, inhibits the inflammatory response in vivo. In view of its important role in inflammation, the purinergic signalling system is bound to yield novel therapeutic opportunities for the treatment of inflammatory diseases.
炎症是一种重要的稳态反应，由一个复杂的相互关联的信号通路网络调控，该网络决定炎症的水平、强度和定位。我们现在知道，嘌呤能信号传导是影响炎症反应起始、进展和下调的信号通路之一。在此，我们综述了嘌呤能信号系统在炎症中作用的最新证据，该系统由细胞外ATP、P2受体和胞外酶级联反应组成。最近利用新开发的生物发光ATP探针（pmeLUC）进行的动物研究能够原位测量细胞周围的ATP，这证明体内炎症组织中存在ATP，其细胞外浓度足以激活P2受体。细胞外ATP水平升高通过P2X7促进白细胞募集和NALP3炎性小体激活，从而在体内放大炎症。例如，通过刺激其分解来降低炎症组织中的细胞外ATP水平，可在体内抑制炎症反应。鉴于其在炎症中的重要作用，嘌呤能信号系统必将为炎症性疾病的治疗带来新的治疗机会。
