Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process.
Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process.
复制标题
巨噬细胞激活和极化改变 P2X7 受体分泌组，影响炎症过程。
DOI：
10.1038/srep22586
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发表时间：
2016-03-03
影响因子：
4.6
通讯作者：
Pelegrín P
中科院分区：
文献类型：
--
作者：
de Torre-Minguela C;Barberà-Cremades M;Gómez AI;Martín-Sánchez F;Pelegrín P
M1极化巨噬细胞上P2X7受体（P2X7R）的激活诱导NLRP3炎性小体的聚集，导致促炎细胞因子的释放和炎症反应的建立。然而，P2X7R向NLRP3炎性体的信号在M2巨噬细胞上是不偶联的，而受体激活没有改变。在本研究中，我们分析了野生型和P2X7R缺陷型巨噬细胞的P2X7R分泌组，证明了P2X7R刺激后释放的蛋白质超出了caspase-1分泌组。p2x7r -分泌组的表征揭示了该受体通过微调蛋白质释放的新功能。我们发现，巨噬细胞中的P2X7R刺激能够释放有效的抗炎蛋白，如膜联蛋白A1，独立于它们的极化状态，这首次表明P2X7R在炎症消退过程中的潜在作用，而与促炎细胞因子的释放无关。这些结果对于开发靶向P2X7R的治疗药物至关重要。
The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R.