Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis
Platelets release proinflammatory microparticles in anti-neutrophil cytoplasmic antibody-associated vasculitis
复制标题
抗中性粒细胞胞浆抗体相关性血管炎中血小板释放促炎微粒
DOI：
10.1093/rheumatology/kez044
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Minghui Zhao
中科院分区：
文献类型：
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作者：
Di Miao;Tiantian Ma;Min Chen;Minghui Zhao
目的导致 ANCA 相关性血管炎 (AAV) 的血小板的生物学功能尚不清楚。本研究旨在探讨血小板衍生微粒（PMP）在 AAV 中的潜在作用。方法在本研究中，通过流式细胞术分析 AAV 患者的微粒，并使用抗体微阵列检测 PMP 中患者血小板分泌的 640 种生物活性蛋白的相对水平。然后将这些数据与临床和病理参数相关。 结果 69 名 AAV 患者中的 PMP 显着增加，主要是活动期 MPO-ANCA 阳性患者，与缓解期相比 [4406.8/μl (2135.4, 5485.0)vs549.7/μl (350, 708.5)，P < 0.0001]，活性 AAV 中微粒含量为 43%是 PMP。与15例缓解期患者相比，15例AAV活动期患者血小板微粒中促炎分子高表达，揭示PMPs的潜在功能是促进趋化、粘附、生长和凋亡作用（芯片分析的所有患者均为MPO-ANCA阳性）。 PMPs的水平与疾病活动性、炎症和肾损伤有显着相关性。结论PMPs可能通过在AAV中广泛产生促炎细胞因子而充当炎症传播者，可能提供新的治疗靶点。
ObjectiveThe biological functions of the platelets contributing to ANCA-associated vasculitis (AAV) are largely unclear. The current study aimed to investigate the potential role of platelet-derived microparticles (PMPs) in AAV.MethodsIn the current study, microparticles in AAV patients were analysed by flow cytometry, and PMPs were probed for relative levels of 640 bioactive proteins secreted from patients’ platelets using antibody microarrays. These data were then correlated with clinical and pathological parameters.ResultsPMPs were significantly increased in 69 AAV patients, predominantly MPO-ANCA positive patients in active stage compared with in remission [4406.8/μl (2135.4, 5485.0)vs549.7/μl (350, 708.5),P < 0.0001], and 43% of microparticles in active AAV were PMPs. Compared with 15 patients in remission, highly expressed proinflammatory molecules in the microparticles from platelets in 15 AAV patients in active stage revealed that potential functions of PMPs were promotion of the effect of chemotaxis, adhesion, growth and apoptosis (all the patients for array analysis were MPO-ANCA positive). The level of PMPs had a significant association with disease activity, inflammation, and renal damage.ConclusionPMPs may serve as inflammatory propagators through their wide production of proinflammatory cytokines in AAV, potentially providing a novel therapeutic target.