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在实验性自身免疫性脑脊髓炎大鼠模型的急性脑炎症期间,通过定量近红外荧光成像在体内监测Cy5.5-Tat标记的T淋巴细胞的命运。

In vivo monitoring the fate of Cy5.5-Tat labeled T lymphocytes by quantitative near-infrared fluorescence imaging during acute brain inflammation in a rat model of experimental autoimmune encephalomyelitis.

作者信息

Berger Cedric, Gremlich Hans-Ulrich, Schmidt Philipp, Cannet Catherine, Kneuer Rainer, Hiestand Peter, Rausch Martin, Rudin Markus

机构信息

Novartis Institutes for Biomedical Research, Basel, Switzerland.

出版信息

J Immunol Methods. 2007 May 31;323(1):65-77. doi: 10.1016/j.jim.2007.02.009. Epub 2007 Mar 22.

Abstract

T cells and macrophages directed against myelin proteins orchestrate the inflammation process in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). So far, assessment of macrophages infiltration or structural alterations has been achieved by in vivo imaging. In this work, we show the infiltration of Cy5.5-labeled T lymphocytes into the brains of EAE rats by reflectance near-infrared fluorescence imaging. T lymphocytes were labeled with Cy5.5-Tat and administered intravenously to naïve or EAE animals. The highest fluorescence signal was observed for EAE animals, which received myelin-activated T cells during the acute phase of the disease. The temporal profile of fluorescence in this group paralleled the pattern of neurological impairment during the acute phase, the remittance and first relapses of EAE. No disease specific fluorescence pattern was observed for EAE animals, which received naïve T cells. However, uptake of Cy5.5-Tat by scavenger cells (e.g. macrophages) following death of labeled T cells in vivo prevents prolonged longitudinal studies. Our work demonstrates that Cy5.5-Tat labeling of T cells is suitable for in vivo fluorescence imaging of inflammation initiation in the EAE model. This approach may particularly be useful for evaluation of novel anti-inflammatory therapies.

摘要

针对髓磷脂蛋白的T细胞和巨噬细胞在多发性硬化症(MS)和实验性自身免疫性脑脊髓炎(EAE)中协调炎症过程。到目前为止,巨噬细胞浸润或结构改变的评估是通过体内成像实现的。在这项工作中,我们通过反射近红外荧光成像展示了Cy5.5标记的T淋巴细胞浸润到EAE大鼠的大脑中。T淋巴细胞用Cy5.5-Tat标记,并静脉注射给未致敏或患有EAE的动物。在疾病急性期接受髓磷脂激活T细胞的EAE动物观察到最高的荧光信号。该组荧光的时间分布与EAE急性期、缓解期和首次复发期间的神经功能缺损模式平行。接受未致敏T细胞的EAE动物未观察到疾病特异性荧光模式。然而,体内标记的T细胞死亡后,清除细胞(如巨噬细胞)对Cy5.5-Tat的摄取妨碍了长期纵向研究。我们的工作表明,T细胞的Cy5.5-Tat标记适用于EAE模型中炎症起始的体内荧光成像。这种方法可能对评估新型抗炎疗法特别有用。

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