Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells.
Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells.
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DOI：
10.1016/j.celrep.2021.110222
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发表时间：
2022-01-11
期刊：
影响因子：
8.8
通讯作者：
Janssen WJ
中科院分区：
文献类型：
--
作者：
McCubbrey AL;McManus SA;McClendon JD;Thomas SM;Chatwin HB;Reisz JA;D'Alessandro A;Mould KJ;Bratton DL;Henson PM;Janssen WJ
凋亡细胞的吞噬作用（称为吞噬作用）对于组织稳态至关重要，并驱动吞噬巨噬细胞中的抗炎程序。在这里，我们评估了幼稚和炎症巨噬细胞吞噬多个细胞和非细胞靶点后的代谢产物。在体外和体内，胞饮作用导致甜菜碱衍生的多胺、亚精胺和精胺增加。令人惊讶的是，多胺积累后，胞饮不产生保留的凋亡细胞代谢产物或从头合成，但从增强多胺进口是依赖于Rac 1，肌动蛋白，和PI 3激酶。阻断多胺输入可防止巨噬细胞白细胞介素（IL）-1β或IL-6抑制性红细胞增多。这确定了巨噬细胞作为多胺输入和积累的触发器，以及输入的多胺作为巨噬细胞诱导的免疫重编程的介质。McCubbrey等人表明，吞噬性巨噬细胞中的细胞内多胺、亚精胺和精胺的积累可导致巨噬细胞内的细胞内多胺、亚精胺和精胺的积累。胞吐作用不增加多胺的合成，但触发多胺的内吞输入。阻断内吞输入可防止胞饮后多胺的积累，并降低胞饮抑制IL-1β和IL-6的能力。
Phagocytosis of apoptotic cells, termed efferocytosis, is critical for tissue homeostasis and drives anti-inflammatory programming in engulfing macrophages. Here, we assess metabolites in naive and inflammatory macrophages following engulfment of multiple cellular and non-cellular targets. Efferocytosis leads to increases in the arginine-derived polyamines, spermidine and spermine, in vitro and in vivo. Surprisingly, polyamine accumulation after efferocytosis does not arise from retention of apoptotic cell metabolites or de novo synthesis but from enhanced polyamine import that is dependent on Rac1, actin, and PI3 kinase. Blocking polyamine import prevents efferocytosis from suppressing macrophage interleukin (IL)-1β or IL-6. This identifies efferocytosis as a trigger for polyamine import and accumulation, and imported polyamines as mediators of efferocytosis-induced immune reprogramming. McCubbrey et al. show that efferocytosis elicits accumulation of intracellular polyamines, spermidine and spermine, in engulfing macrophages. Efferocytosis does not increase polyamine synthesis but triggers endocytic import of polyamines. Blocking endocytic import prevents polyamine accumulation after efferocytosis and reduces the ability of efferocytosis to suppress IL-1β and IL-6.
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影响因子：
8.8
作者：
Gobert AP;Finley JL;Latour YL;Asim M;Smith TM;Verriere TG;Barry DP;Allaman MM;Delagado AG;Rose KL;Calcutt MW;Schey KL;Sierra JC;Piazuelo MB;Mirmira RG;Wilson KT
通讯作者：
Wilson KT
影响因子：
4
作者：
Catala, Alexis;Youssef, Lyla A.;D'Alessandro, Angelo
通讯作者：
D'Alessandro, Angelo
DOI：
10.1038/s41568-018-0050-3
发表时间：
2018-11
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Casero RA Jr;Murray Stewart T;Pegg AE
通讯作者：
Pegg AE
影响因子：
15.9
作者：
Fond, Aaron M.;Lee, Chang Sup;Ravichandran, Kodi S.
通讯作者：
Ravichandran, Kodi S.
影响因子：
7.3
作者：
Burns, Mark R.;Graminski, Gerard F.;O'Brien, Thomas G.
通讯作者：
O'Brien, Thomas G.