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体外生成的血小板衍生微粒类似于类风湿关节炎患者的循环囊泡,并激活单核细胞。

Platelet-derived microparticles generated in vitro resemble circulating vesicles of patients with rheumatoid arthritis and activate monocytes.

机构信息

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.

Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia; Unidad de Citometría de Flujo, Sede de Investigación Universitaria, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, Colombia.

出版信息

Cell Immunol. 2019 Feb;336:1-11. doi: 10.1016/j.cellimm.2018.12.002. Epub 2018 Dec 4.

DOI:10.1016/j.cellimm.2018.12.002
PMID:30538031
Abstract

Patients with rheumatoid arthritis (RA) have increased amount of platelet-derived microparticles (PMPs) positive for citrullinated peptides (CPs) that form immune complexes (PMPs-ICs). Monocytes are important inflammatory mediators that play a role in the clearance of PMPs-ICs. We aimed to generate PMPs-ICs in vitro and determine its effect on monocytes from patients with RA and healthy individuals (HI). PMPs from patients showed platelet markers, mitochondria content, and phosphatidylserine exposure similar to PMPs from HI. However, patients had a higher frequency of IgG+ and CPs+ vesicles than HI. PMPs-ICs generated in vitro were similar to the circulating vesicles of patients with respect to IgG- and CPs-positivity. PMPs-ICs induced pro-inflammatory cytokines and CX3CR1 expression in monocytes from HI, and IL-10 and CD36 upregulation in monocytes from patients. These results suggest that PMPs-ICs induce activation of monocytes, with a pro-inflammatory response in HI and a more tolerant response in cells of patients with RA.

摘要

类风湿关节炎(RA)患者的血小板衍生微粒(PMP)中存在大量的瓜氨酸化肽(CP)阳性的免疫复合物(PMP-IC)。单核细胞是重要的炎症介质,在清除 PMP-IC 中发挥作用。我们旨在体外生成 PMP-ICs,并确定其对 RA 患者和健康个体(HI)单核细胞的影响。与 HI 的 PMP 相比,患者的 PMP 显示出血小板标志物、线粒体含量和磷脂酰丝氨酸暴露相似。然而,患者的 IgG+和 CPs+小泡的频率高于 HI。体外生成的 PMP-ICs在 IgG-和 CPs 阳性方面与患者的循环小泡相似。PMP-ICs 诱导 HI 单核细胞中促炎细胞因子和 CX3CR1 的表达,以及患者单核细胞中 IL-10 和 CD36 的上调。这些结果表明,PMP-ICs 诱导单核细胞活化,在 HI 中引起促炎反应,在 RA 患者的细胞中引起更耐受的反应。

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