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利用层流系统、生物信息学跟踪和转录组分析分析恶性疟原虫感染的红细胞与人内皮细胞的相互作用。

Analysis of the Interaction Between Plasmodium falciparum-Infected Erythrocytes and Human Endothelial Cells Using a Laminar Flow System, Bioinformatic Tracking and Transcriptome Analysis.

机构信息

Bernhard Nocht Institut for Tropical Medicine, Hamburg, Germany.

出版信息

Methods Mol Biol. 2021;2369:187-197. doi: 10.1007/978-1-0716-1681-9_11.

Abstract

During malaria infection, the endothelial lining of the small blood vessels of the brain and other vital organs is strongly stimulated. This leads to fatal complications and poor prognosis of the infection. It is believed that two main reasons are responsible for this pathology, namely the cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) on the one hand and the proinflammatory products released by the IEs which activate the endothelial cells (ECs) on the other hand. Until recently, most of the studies that characterized the activation of ECs were performed under static conditions, which do not reflect the real sequelae in vivo. In this chapter, we present a system, which allows authentic simulation of the IEs-ECs interactions during P. falciparum infection.The main idea of the system is to provide an adequate shear stress over the ECs during the cytoadhesion and stimulation with IEs, which provides a better basis for the investigation of the cytoadhesion pathology through analyzing the ECs' transcriptome after stimulation. On the other hand, analyzing the transcriptome of the IEs might also give deeper analysis of their response to shear stress. Deep understanding of these events might help in the development of novel treatment strategies that interfere with this cell-cell interaction.

摘要

在疟疾感染期间,大脑和其他重要器官的小血管的内皮衬里受到强烈刺激。这导致了致命的并发症和感染的不良预后。据信,有两个主要原因导致这种病理学,一方面是恶性疟原虫感染的红细胞(IEs)与内皮细胞(ECs)的细胞黏附,另一方面是 IEs 释放的促炎产物激活 ECs。直到最近,大多数描述 ECs 激活的研究都是在静态条件下进行的,这些条件并不能反映体内的真实后果。在本章中,我们提出了一个系统,该系统允许在恶性疟原虫感染期间对 IEs-ECs 相互作用进行真实模拟。该系统的主要思想是在细胞黏附和 IEs 刺激过程中为 ECs 提供足够的切应力,这为通过分析刺激后 ECs 的转录组来分析细胞黏附病理学提供了更好的基础。另一方面,分析 IEs 的转录组也可能对它们对切应力的反应进行更深入的分析。深入了解这些事件可能有助于开发新的治疗策略,以干扰这种细胞-细胞相互作用。

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