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用于M2巨噬细胞门控定向活细胞区分的荧光探针的开发

Development of a Fluorescent Probe for M2 Macrophages Gating-Oriented Live-Cell Distinction.

作者信息

Cho Heewon, Kwon Haw-Young, Lee Sun Hyeok, Lee Hong-Guen, Kang Nam-Young, Chang Young-Tae

机构信息

School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.

Center for Self-assembly and Complexity, Institute for Basic Science (IBS), Pohang 37673, Republic of Korea.

出版信息

J Am Chem Soc. 2023 Feb 8;145(5):2951-2957. doi: 10.1021/jacs.2c11393. Epub 2023 Jan 27.

Abstract

Macrophages are the most plastic immune cells by changing their characters in response to environmental stimuli. Broadly, macrophages are categorized into two different subsets based on M1/M2 paradigm, which exhibit completely contrary phenotypes. Whereas M1 macrophages are aggressive to offend invaders such as bacteria and tumors, M2 are anti-inflammatory cells and seemingly help tumor immunity. Tumor-associated macrophages are typical examples of M2 cells as the key components of forming and maintaining the tumor microenvironment. Despite the intensive interest, monitoring M2 macrophages in real time is hampered by the lack of competent detection tools. Here, we report the first M2 selective probe with a novel mechanism of gating-oriented live-cell distinction through M2-favored fatty acid transporters. To demonstrate the potential of , we visualize the progressive phenotypic change of M2 toward M1 using a resveratrol analogue HS-1793 as a reprogramming effector. Combined together with M1 probe , the diminishing M2 character and emerging M1 markers could be simultaneously monitored in real time through the multicolor changes during macrophage reprogramming.

摘要

巨噬细胞是最具可塑性的免疫细胞,能够根据环境刺激改变其特性。广义上讲,巨噬细胞根据M1/M2范式可分为两个不同的亚群,它们表现出完全相反的表型。M1巨噬细胞具有攻击性,可抵御细菌和肿瘤等入侵者,而M2巨噬细胞是抗炎细胞,似乎有助于肿瘤免疫。肿瘤相关巨噬细胞是M2细胞的典型例子,是形成和维持肿瘤微环境的关键组成部分。尽管人们对此兴趣浓厚,但由于缺乏有效的检测工具,实时监测M2巨噬细胞仍受到阻碍。在此,我们报告了首个M2选择性探针,它通过M2偏好的脂肪酸转运蛋白,以一种新型的门控导向活细胞区分机制发挥作用。为了证明该探针的潜力,我们使用白藜芦醇类似物HS-1793作为重编程效应物,可视化了M2向M1的渐进性表型变化。与M1探针结合,通过巨噬细胞重编程过程中的多色变化,可以实时同时监测M2特性的减弱和M1标志物的出现。

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