ATP release and purinergic signaling in NLRP3 inflammasome activation.
ATP release and purinergic signaling in NLRP3 inflammasome activation.
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DOI：
10.3389/fimmu.2012.00414
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发表时间：
2012
影响因子：
7.3
通讯作者：
Couillin I
中科院分区：
文献类型：
--
作者：
Gombault A;Baron L;Couillin I
NLRP 3炎性体是一种参与IL-1β和IL-18加工的蛋白质复合物，可感知病原体和病原体相关的分子模式（PAMP和DAMP）。已经提出了一步或两步模型来解释炎症期间IL-1β产生的严格调节。此外，细胞刺激触发三磷酸腺苷（ATP）释放和随后激活细胞表面的嘌呤能受体。重要的是，一些研究已经报道了细胞外ATP在响应PAMP和DAMP的NLRP 3炎性体活化中的作用。在这篇简短的综述中，我们将讨论主动ATP释放，嘌呤能信号和NLRP 3炎性小体激活之间的联系。我们将重点关注自分泌或旁分泌ATP输出在颗粒诱导的NLRP 3炎性体激活中的作用，并讨论颗粒激活剂如何能够通过一个过程诱导IL-1β的成熟和分泌，该过程涉及，作为第一个事件，通过半通道开放的内源性ATP的细胞外释放，作为第二个事件，通过触发NLRP 3炎性体激活的嘌呤能受体进行信号传导。最后，我们将回顾ATP作为死亡细胞释放的关键促炎介质的证据。特别是，我们将讨论如何通过自噬死亡的癌细胞触发吞噬它们的巨噬细胞中的ATP依赖性NLRP 3炎性小体激活，引发针对肿瘤的免疫原性反应。
The NLRP3 inflammasome is a protein complex involved in IL-1β and IL-18 processing that senses pathogen- and danger-associated molecular patterns (PAMPs and DAMPs). One step- or two step-models have been proposed to explain the tight regulation of IL-1β production during inflammation. Moreover, cellular stimulation triggers adenosine triphosphate (ATP) release and subsequent activation of purinergic receptors at the cell surface. Importantly some studies have reported roles for extracellular ATP, in NLRP3 inflammasome activation in response to PAMPs and DAMPs. In this mini review, we will discuss the link between active ATP release, purinergic signaling and NLRP3 inflammasome activation. We will focus on the role of autocrine or paracrine ATP export in particle-induced NLRP3 inflammasome activation and discuss how particle activators are competent to induce maturation and secretion of IL-1β through a process that involves, as a first event, extracellular release of endogenous ATP through hemichannel opening, and as a second event, signaling through purinergic receptors that trigger NLRP3 inflammasome activation. Finally, we will review the evidence for ATP as a key pro-inflammatory mediator released by dying cells. In particular we will discuss how cancer cells dying via autophagy trigger ATP-dependent NLRP3 inflammasome activation in the macrophages engulfing them, eliciting an immunogenic response against tumors.