ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages.
ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages.
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DOI：
10.1371/journal.pone.0040069
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fésüs L
中科院分区：
文献类型：
--
作者：
Ayna G;Krysko DV;Kaczmarek A;Petrovski G;Vandenabeele P;Fésüs L
病原体激活和损伤相关的分子模式激活巨噬细胞中的炎性小体。我们报道了小鼠巨噬细胞在与pro-B（Ba/F3）细胞共孵育时释放IL-1β，所述pro-B（Ba/F3）细胞由于IL-3撤回而通过凋亡和自噬而死亡，但当它们与活的、凋亡的、坏死的或坏死抑制素-1处理的细胞共孵育时不释放IL-1β。NALP 3缺陷型巨噬细胞显示IL-1β分泌减少，这在半胱天冬酶-1缺陷型或用其抑制剂预处理的巨噬细胞中也受到抑制。这一发现表明炎性小体在吞噬垂死的自噬细胞过程中被激活。我们发现NALP 3的激活依赖于死亡细胞的吞噬作用、通过死亡自噬细胞的泛连接蛋白-1通道的ATP释放、P2 X7嘌呤能受体激活以及随后的钾外流。在小鼠中腹膜内注射死亡的自噬Ba/F3细胞募集中性粒细胞，从而诱导急性炎症。这些发现表明，NALP 3在吞噬垂死自噬细胞的小鼠巨噬细胞中的炎性小体激活中发挥关键的上游功能，并且这些功能导致促炎反应。
Pathogen-activated and damage-associated molecular patterns activate the inflammasome in macrophages. We report that mouse macrophages release IL-1β while co-incubated with pro-B (Ba/F3) cells dying, as a result of IL-3 withdrawal, by apoptosis with autophagy, but not when they are co-incubated with living, apoptotic, necrotic or necrostatin-1 treated cells. NALP3-deficient macrophages display reduced IL-1β secretion, which is also inhibited in macrophages deficient in caspase-1 or pre-treated with its inhibitor. This finding demonstrates that the inflammasome is activated during phagocytosis of dying autophagic cells. We show that activation of NALP3 depends on phagocytosis of dying cells, ATP release through pannexin-1 channels of dying autophagic cells, P2X7 purinergic receptor activation, and on consequent potassium efflux. Dying autophagic Ba/F3 cells injected intraperitoneally in mice recruit neutrophils and thereby induce acute inflammation. These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
3.1
作者：
ELLIOTT, JA;WINN, WC
通讯作者：
WINN, WC
DOI：
10.1084/jem.20100257
发表时间：
2010-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Broz P;Newton K;Lamkanfi M;Mariathasan S;Dixit VM;Monack DM
通讯作者：
Monack DM
影响因子：
12.4
作者：
Gozuacik, D.;Bialik, S.;Kimchi, A.
通讯作者：
Kimchi, A.
影响因子：
4.8
作者：
Krysko, Dmitri V.;Vanden Berghe, Tom;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter