Functional significance of macrophage-derived exosomes in inflammation and pain.
Functional significance of macrophage-derived exosomes in inflammation and pain.
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DOI：
10.1016/j.pain.2014.04.029
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发表时间：
2014-08
期刊：
影响因子：
7.4
通讯作者：
Ajit SK
中科院分区：
文献类型：
--
作者：
McDonald MK;Tian Y;Qureshi RA;Gormley M;Ertel A;Gao R;Aradillas Lopez E;Alexander GM;Sacan A;Fortina P;Ajit SK
外泌体是一种分泌的微囊泡，通过体液转运微小RNA（miRNA）、mRNA和蛋白质，促进细胞间通讯并引发免疫应答。外泌体含量取决于细胞的来源和生理条件，并且可以提供对细胞和系统如何科普生理扰动的见解。先前对复杂区域疼痛综合征（CRPS）患者（一种使人衰弱的慢性疼痛疾病）循环miRNA的分析显示，全血中的一部分miRNA在疾病中发生了改变。为了确定外泌体生物分子在炎症和疼痛中的改变的功能后果，我们研究了外泌体介导的体外信息传递，在炎性疼痛的啮齿动物模型和CRPS患者的外泌体中。用脂多糖（LPS）刺激的小鼠巨噬细胞分泌含有高水平细胞因子和介导炎症的miRNA的外泌体。外泌体RNA的转录组测序揭示了先天性和适应性免疫途径的全局改变。来自LPS刺激的细胞的外泌体足以引起幼稚细胞中的NF-κ B活化，表明受体细胞中的功能性。在炎症性疼痛的小鼠模型中，单次注射外泌体减弱了热痛觉过敏，表明巨噬细胞来源的外泌体具有免疫保护作用。我们还表明，复杂区域疼痛综合征患者中改变的循环miRNA是由外泌体运输的。巨噬细胞来源的外泌体携带保护性特征，当分泌细胞暴露于炎症刺激时，该特征发生改变。由于它们的系统信号传导能力，外泌体可以诱导多效性效应，可能介导慢性疼痛的多因素病理学，并且应该探索它们的治疗效用。
Exosomes, secreted microvesicles transporting microRNAs (miRNAs), mRNAs, and proteins through bodily fluids, facilitate intercellular communication and elicit immune responses. Exosomal contents vary depending on the source and the physiological conditions of cells and can provide insights into how cells and systems cope with physiological perturbations. Previous analysis of circulating miRNAs in patients with complex regional pain syndrome (CRPS), a debilitating chronic pain disorder, revealed a subset of miRNAs in whole blood that are altered in the disease. To determine functional consequences of alterations in exosomal biomolecules in inflammation and pain, we investigated exosome-mediated information transfer in vitro, in a rodent model of inflammatory pain and in exosomes from patients with CRPS. Mouse macrophage cells stimulated with lipopolysaccharides (LPS) secrete exosomes containing elevated levels of cytokines and miRNAs that mediate inflammation. Transcriptome sequencing of exosomal RNA revealed global alterations in both innate and adaptive immune pathways. Exosomes from LPS-stimulated cells were sufficient to cause NF-kappaB activation in naïve cells, indicating functionality in recipient cells. A single injection of exosomes attenuated thermal hyperalgesia in a mouse model of inflammatory pain, suggesting an immunoprotective role for macrophage-derived exosomes. We also show that circulating miRNAs altered in patients with complex regional pain syndrome are trafficked by exosomes. Macrophage-derived exosomes carry a protective signature that is altered when secreting cells are exposed to an inflammatory stimulus. With their systemic signaling capabilities, exosomes can induce pleiotropic effects potentially mediating the multifactorial pathology underlying chronic pain and should be explored for their therapeutic utility.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
7.4
作者：
Harden NR;Bruehl S;Perez RSGM;Birklein F;Marinus J;Maihofner C;Lubenow T;Buvanendran A;Mackey S;Graciosa J;Mogilevski M;Ramsden C;Chont M;Vatine JJ
通讯作者：
Vatine JJ
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
4.5
作者：
Beatty, WL;Rhoades, ER;Russell, DG
通讯作者：
Russell, DG