Morandini Ana Carolina, Savio Luiz Eduardo Baggio, Coutinho-Silva Robson
Immunobiology Program, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro; National Institute of Science and Technology for Translational Research in Health and Environment in the Amazon Region (INPeTAm), Rio de Janeiro, RJ, Brazil.
Biomed J. 2014 Jul-Aug;37(4):169-77. doi: 10.4103/2319-4170.127803.
The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is ubiquitously expressed in almost all tissues and organs of the body with the highest distribution in the immune cells of monocyte-macrophage origin. Classically, P2X7 receptor is involved in apoptotic cell death, and it is well known that extracellular ATP ligation to this purinergic receptor serves as an important secondary stimulus, which is also considered as danger signal for the interleukin (IL)-1β cleavage and secretion from pro-inflammatory cells. More recently, however, there has been substantial evidence of additional roles for the P2X7 receptor, both in innate immune response and as an adaptive link, including T-cell activation in a chronic state of inflammation. Also, compelling evidences have revealed an important role for ectonucleotidases as ATP-consuming enzymes in the control and fine-tuning of P2X7 function by regulating the time, concentration, and availability of ATP during infection-driven inflammation. This review focuses on the current evidences for P2X7 receptor involvement in the initial stages of inflammation, as well as for its role in acute and chronic stages of infection. Here, we also highlight the role of ectonucleotidase family in the control of P2X7 function, including the initial and resolution phases of inflammation.
嘌呤能受体P2X配体门控离子通道7(P2X7)在人体几乎所有组织和器官中均有广泛表达,在单核细胞 - 巨噬细胞来源的免疫细胞中分布最高。传统上,P2X7受体参与凋亡性细胞死亡,众所周知,细胞外ATP与该嘌呤能受体结合是一种重要的次级刺激,它也被认为是促炎细胞中白细胞介素(IL)-1β裂解和分泌的危险信号。然而,最近有大量证据表明P2X7受体在先天免疫反应以及作为适应性联系方面具有额外作用,包括在慢性炎症状态下的T细胞活化。此外,令人信服的证据表明,外核苷酸酶作为消耗ATP的酶,在感染驱动的炎症过程中通过调节ATP的时间、浓度和可用性,在P2X7功能的控制和微调中发挥重要作用。本综述重点关注P2X7受体参与炎症初始阶段的当前证据,以及其在感染急性和慢性阶段的作用。在此,我们还强调了外核苷酸酶家族在控制P2X7功能中的作用,包括炎症的初始和消退阶段。