Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients Prevent the Inflammatory Activation of Macrophages.
Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients Prevent the Inflammatory Activation of Macrophages.
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DOI：
10.1016/j.ebiom.2018.02.003
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发表时间：
2018-03
期刊：
影响因子：
11.1
通讯作者：
Perretti M
中科院分区：
文献类型：
--
作者：
Rhys HI;Dell'Accio F;Pitzalis C;Moore A;Norling LV;Perretti M
微泡（MV）正在成为一种新的手段，制定细胞间通信的炎症。在这里，我们的目的是确定嗜中性粒细胞衍生的MV调节靶细胞行为的能力，重点是巨噬细胞。MV是由健康对照中性粒细胞或类风湿性关节炎患者的中性粒细胞对肿瘤坏死因子-α的反应产生的。MV用于体外刺激人单核细胞衍生的巨噬细胞，或在关节炎的K/BxN小鼠模型中关节内施用。使用巨噬细胞/成纤维细胞样滑膜细胞共培养系统来研究囊泡对这些细胞之间的串扰的影响。我们证明了由MV暴露的磷脂酰丝氨酸和膜联蛋白-A1的直接作用，以分别抵消巨噬细胞的经典活化和促进转化生长因子-β的释放。经典活化的巨噬细胞暴露于中性粒细胞MV不再激活成纤维细胞样滑膜细胞在随后的共培养设置。最后，关节炎小鼠关节内给予类风湿性关节炎患者的中性粒细胞MV影响了关节巨噬细胞的表型。总之，这些数据以及特定MV决定簇的鉴定为调节滑膜中正在进行的炎症提供了新的机会-主要是通过影响巨噬细胞极化和潜在的成纤维细胞样滑膜细胞-通过递送由中性粒细胞产生的自体或异源MV。中性粒细胞微泡通过向Mer呈递磷脂酰丝氨酸来限制巨噬细胞的炎性激活。在中性粒细胞微泡上表达的膜联蛋白A1通过激活FPR 2诱导巨噬细胞释放TGFβ。神经元微泡限制巨噬细胞激活成纤维细胞样滑膜细胞的能力。所有的细胞都会释放出小的球形信息包，称为囊泡，它们用来在彼此之间发送信号。一种免疫细胞类型，嗜中性粒细胞，已被证明可以释放囊泡，防止其他免疫细胞变得过度活跃：在这里，我们专注于类风湿性关节炎。这篇论文表明，从中性粒细胞释放的囊泡能够防止另一种免疫细胞类型，巨噬细胞，被激活。重要的是，这种机制是自然发生的，如果我们能够理解它，我们就可以使用我们自己的身体机制来控制慢性炎症。
Microvesicles (MVs) are emerging as a novel means to enact cell-to-cell communication in inflammation. Here, we aimed to ascertain the ability of neutrophil-derived MVs to modulate target cell behaviour, the focus being the macrophage. MVs were generated in response to tumour necrosis factor-α, from healthy control neutrophils or those from rheumatoid arthritis patients. MVs were used to stimulate human monocyte-derived macrophages in vitro, or administered intra-articularly in the K/BxN mouse model of arthritis. A macrophage/fibroblast-like synoviocyte co-culture system was used to study the effects of vesicles on the crosstalk between these cells. We demonstrate a direct role for phosphatidylserine and annexin-A1 exposed by the MVs to counteract classical activation of the macrophages, and promote the release of transforming growth factor-β, respectively. Classically-activated macrophages exposed to neutrophil MVs no longer activated fibroblast-like synoviocytes in subsequent co-culture settings. Finally, intra-articular administration of neutrophil MVs from rheumatoid arthritis patients in arthritic mice affected the phenotype of joint macrophages. Altogether these data, with the identification of specific MV determinants, open new opportunities to modulate on-going inflammation in the synovia – mainly by affecting macrophage polarization and potentially also fibroblast-like synoviocytes - through the delivery of autologous or heterologous MVs produced from neutrophils. Neutrophil microvesicles restrict the inflammatory activation of macrophages by presenting phosphatidylserine to Mer. Annexin A1 expressed on neutrophil microvesicles induces macrophage release of TGFβ by activating FPR2. Neutrophil microvesicles restrict the ability of macrophages to activate fibroblast-like synoviocytes. All cells release small, spherical parcels of information, called vesicles, that they use to send signals between each other. One immune cell type, the neutrophil, has been shown to release vesicles which prevents other immune cells from becoming hyperactive: herein we focus on rheumatoid arthritis. This paper demonstrates that vesicles released from neutrophils are able to prevent another immune cell type, the macrophage, from becoming activated. The importance of this is that this mechanism is occurring naturally, and if we can understand it, we may be able to use our own bodies' mechanisms to control chronic inflammation.
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在类风湿滑膜滑膜成纤维细胞激活IL-17和TNFALPHA后，长时间的粒细胞巨噬细胞刺激性刺激因子依赖性，中性粒细胞存活。
影响因子：
4.9
作者：
Parsonage, Greg;Filer, Andrew;Bik, Magdalena;Hardie, Debbie;Lax, Sian;Howlett, Katherine;Church, Leigh D.;Raza, Karim;Wong, See-Heng;Trebilcock, Emily;Scheel-Toellner, Dagmar;Salmon, Mike;Lord, Janet M.;Buckley, Christopher D.
通讯作者：
Buckley, Christopher D.
影响因子：
15.9
作者：
GUERNE, PA;ZURAW, BL;LOTZ, M
通讯作者：
LOTZ, M
DOI：
10.4049/jimmunol.1301945
发表时间：
2014-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McCauley LK;Dalli J;Koh AJ;Chiang N;Serhan CN
通讯作者：
Serhan CN
影响因子：
4.6
作者：
Headland SE;Jones HR;D'Sa AS;Perretti M;Norling LV
通讯作者：
Norling LV
影响因子：
20.3
作者：
Dalli, Jesmond;Norling, Lucy V.;Perretti, Mauro
通讯作者：
Perretti, Mauro