Liu Yiyun, Zhang Ruyuan, Qu Hongping, Wu Jun, Li Lei, Tang Yaoqing
Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Mol Med Rep. 2017 Mar;15(3):1291-1296. doi: 10.3892/mmr.2017.6113. Epub 2017 Jan 12.
Endothelial microparticles (EMPs) and endothelial cells (ECs) are involved in the pathophysiological mechanisms of sepsis and septic shock. EMPs are small vesicles released by ECs and are considered biomarkers for endothelial cell function and mediators for intercellular information exchange. However, the effect of EMPs on their parental ECs remains unknown. The present study collected tumor necrosis factor‑α‑derived EMPs and detected the proinflammatory cytokines released from unstimulated and EMP‑stimulated ECs by proteome profiler array. This revealed that EMPs induce an inflammatory response in ECs. Within this response, interferon γ‑induced protein 10 was revealed by ELISA to be associated with the activity of EMPs in a time‑ and dose‑dependent manner. It was hypothesized that the possible mechanism underlying this phenomenon was nuclear factor‑κB. This was demonstrated to be crucial for the expression of IP‑10 in EMP‑stimulated ECs and the function of EMPs by immunofluorescence and western blot analysis. The present study enhances understanding of the involvement of EMPs and ECs in sepsis and will assist with the early diagnosis and treatment of sepsis.
内皮微粒(EMPs)和内皮细胞(ECs)参与脓毒症和脓毒性休克的病理生理机制。EMPs是由ECs释放的小囊泡,被认为是内皮细胞功能的生物标志物和细胞间信息交换的介质。然而,EMPs对其母代ECs的影响仍不清楚。本研究收集了肿瘤坏死因子-α衍生的EMPs,并通过蛋白质组分析阵列检测了未刺激和EMPs刺激的ECs释放的促炎细胞因子。这表明EMPs可诱导ECs产生炎症反应。在该反应中,通过酶联免疫吸附测定法发现,γ-干扰素诱导蛋白10与EMPs的活性呈时间和剂量依赖性相关。据推测,这一现象的潜在机制可能是核因子-κB。通过免疫荧光和蛋白质印迹分析证明,核因子-κB对于EMPs刺激的ECs中IP-10的表达以及EMPs的功能至关重要。本研究增进了对EMPs和ECs参与脓毒症的理解,并将有助于脓毒症的早期诊断和治疗。