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环境物质造成的质膜损伤会增强细胞间融合并损害巨噬细胞的免疫功能。

Plasma Membrane Damage by Environmental Materials Enhances Cell-Cell Fusion and Impairs Immune Functions of Macrophages.

作者信息

Wu Dandan, Zhang Xing, Wang Ruoning, Livingston Amanda, El Hayek Eliane, Xue Xiang, Neumann Aaron, Campen Matthew, Liu Meilian, Yang Xuexian O

机构信息

Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.

Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.

出版信息

bioRxiv. 2025 Jun 23:2025.06.17.660197. doi: 10.1101/2025.06.17.660197.

DOI:10.1101/2025.06.17.660197
PMID:40667368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12262220/
Abstract

Macrophages are the most abundant phagocytes and play an essential role in host defense. Previous studies have shown that many environmental materials can activate macrophages and trigger inflammatory responses. However, whether these exposures alter macrophage function in host defense remains unclear. This study found that many environmental materials (such as carbon nanotubes, tungsten carbide [WC], and detergents) can damage the plasma membranes of macrophages. This damage leads to decreased reactive oxygen species (ROS) production and phagocytosis but elevated cell-cell fusion. In vivo, airway exposure to laundry detergent impaired the recruitment of macrophages and other myeloid cells to the lung and dramatically dampened protective TH1 and TH17 cell responses, leading to increased susceptibility to Candida infection in mice. Overall, our data indicate that exposure to environmental materials compromises macrophage membrane integrity and impairs host defense. These findings may aid in the development of effective preventive and therapeutic strategies.

摘要

巨噬细胞是最丰富的吞噬细胞,在宿主防御中发挥着至关重要的作用。先前的研究表明,许多环境物质可激活巨噬细胞并引发炎症反应。然而,这些暴露是否会改变巨噬细胞在宿主防御中的功能仍不清楚。本研究发现,许多环境物质(如碳纳米管、碳化钨[WC]和洗涤剂)可损伤巨噬细胞的质膜。这种损伤导致活性氧(ROS)产生减少和吞噬作用降低,但细胞间融合增加。在体内,气道暴露于洗衣粉会损害巨噬细胞和其他髓样细胞向肺部的募集,并显著抑制保护性TH1和TH17细胞反应,导致小鼠对念珠菌感染的易感性增加。总体而言,我们的数据表明,暴露于环境物质会损害巨噬细胞膜完整性并损害宿主防御。这些发现可能有助于制定有效的预防和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/78904588a879/nihpp-2025.06.17.660197v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/4c0c1ad0eee5/nihpp-2025.06.17.660197v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/712f00eeb3ca/nihpp-2025.06.17.660197v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/213551c1fb03/nihpp-2025.06.17.660197v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/c231370d1380/nihpp-2025.06.17.660197v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/296137c122aa/nihpp-2025.06.17.660197v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/78904588a879/nihpp-2025.06.17.660197v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/4c0c1ad0eee5/nihpp-2025.06.17.660197v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/712f00eeb3ca/nihpp-2025.06.17.660197v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/213551c1fb03/nihpp-2025.06.17.660197v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/c231370d1380/nihpp-2025.06.17.660197v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/296137c122aa/nihpp-2025.06.17.660197v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/343d/12262220/78904588a879/nihpp-2025.06.17.660197v1-f0006.jpg

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本文引用的文献

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Cell fusion dynamics: mechanisms of multinucleation in osteoclasts and macrophages.细胞融合动力学:破骨细胞和巨噬细胞多核化的机制
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Multinucleation resets human macrophages for specialized functions at the expense of their identity.多核化会重置人类巨噬细胞以执行特殊功能,但代价是牺牲其细胞特性。
EMBO Rep. 2023 Apr 5;24(4):e57070. doi: 10.15252/embr.202357070.
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