Necrotic cardiac myocytes skew macrophage polarization towards a classically activated phenotype.
Necrotic cardiac myocytes skew macrophage polarization towards a classically activated phenotype.
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DOI：
10.1371/journal.pone.0282921
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
坏死和垂死的细胞释放损伤相关分子模式（DAMP），可以启动心脏中的无菌炎症反应。尽管巨噬细胞对于心肌修复和再生是必不可少的，但DAMP对巨噬细胞活化的影响仍不清楚。为了解决这一知识空白，我们研究了坏死心肌细胞提取物对体外原代腹膜巨噬细胞（PPM）培养的影响。我们首先对在存在和不存在以下物质的情况下培养长达72小时的PPM进行无偏转录组学分析：1）来自坏死心肌细胞的坏死细胞提取物（NCE），以模拟DAMP的释放; 2）脂多糖（LPS），已知其使巨噬细胞朝向经典活化表型活化，和3）白细胞介素-4（IL-4），已知其可促进巨噬细胞向替代活化表型极化。NCE引起差异基因表达（DEG）的变化，与LPS诱导的变化有相当大的重叠，表明NCE促进巨噬细胞向经典活化表型极化。用蛋白酶-K处理NCE消除了NCE对巨噬细胞活化的影响，而用DNA酶和RNA酶处理NCE不影响巨噬细胞活化。用NCE和LPS刺激巨噬细胞培养物导致巨噬细胞吞噬作用和白细胞介素-1 β分泌显著增加，而用IL-4处理对吞噬作用和白细胞介素-1 β无显著影响。总之，我们的研究结果表明，从坏死心肌细胞释放的蛋白质足以使巨噬细胞的极化向经典活化表型倾斜。
Necrotic and dying cells release damage-associated molecular patterns (DAMPs) that can initiate sterile inflammatory responses in the heart. Although macrophages are essential for myocardial repair and regeneration, the effect of DAMPs on macrophage activation remains unclear. To address this gap in knowledge we studied the effect of necrotic cardiac myocyte extracts on primary peritoneal macrophage (PPM) cultures in vitro. We first performed unbiased transcriptomic profiling with RNA-sequencing of PPMs cultured for up to 72 hours in the presence and absence of: 1) necrotic cell extracts (NCEs) from necrotic cardiac myocytes in order to mimic the release of DAMPs; 2) lipopolysaccharide (LPS), which is known to polarize macrophages towards a classically activated phenotype and 3) Interleukin-4 (IL-4), which is known to promote polarization of macrophages towards an alternatively activated phenotype. NCEs provoke changes in differential gene expression (DEGs) that had considerable overlap with LPS-induced changes, suggesting that NCEs promote macrophage polarization towards a classically activated phenotype. Treating NCEs with proteinase-K abolished the effects of NCEs on macrophage activation, whereas NCE treatment with DNase and RNase did not affect macrophage activation. Stimulation of macrophage cultures with NCEs and LPS resulted in a significant increase in macrophage phagocytosis and interleukin-1β secretion, whereas treatment with IL-4 had no significant effect on phagocytosis and interleukin-1β. Taken together, our findings suggest that proteins released from necrotic cardiac myocytes are sufficient to skew the polarization of macrophages towards a classically activated phenotype.
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影响因子：
3.7
作者：
Jablonski KA;Amici SA;Webb LM;Ruiz-Rosado Jde D;Popovich PG;Partida-Sanchez S;Guerau-de-Arellano M
通讯作者：
Guerau-de-Arellano M
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.4
作者：
Epelman, Slava;Mann, Douglas L.
通讯作者：
Mann, Douglas L.
DOI：
10.1084/jem.176.1.287
发表时间：
1992-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Stein M;Keshav S;Harris N;Gordon S
通讯作者：
Gordon S
影响因子：
64.8
作者：
West, A. Phillip;Brodsky, Igor E.;Rahner, Christoph;Woo, Dong Kyun;Erdjument-Bromage, Hediye;Tempst, Paul;Walsh, Matthew C.;Choi, Yongwon;Shadel, Gerald S.;Ghosh, Sankar
通讯作者：
Ghosh, Sankar