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锌加速人 PMN 呼吸爆发的终止。

Zinc accelerates respiratory burst termination in human PMN.

机构信息

Center of Physiology, Pathophysiology and Biophysics, Paracelsus Medical University, Nuremberg, Germany; Department of Gynecology and Obstetrics, Johannes Gutenberg University, Mainz, Germany.

Center of Physiology, Pathophysiology and Biophysics, Paracelsus Medical University, Nuremberg, Germany.

出版信息

Redox Biol. 2021 Nov;47:102133. doi: 10.1016/j.redox.2021.102133. Epub 2021 Sep 17.

DOI:10.1016/j.redox.2021.102133
PMID:34562872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8476447/
Abstract

The respiratory burst of phagocytes is essential for human survival. Innate immune defence against pathogens relies strongly on reactive oxygen species (ROS) production by the NADPH oxidase (NOX2). ROS kill pathogens while the translocation of electrons across the plasma membrane via NOX2 depolarizes the cell. Simultaneously, protons are released into the cytosol. Here, we compare freshly isolated human polymorphonuclear leukocytes (PMN) to the granulocytes-like cell line PLB 985. We are recording ROS production while inhibiting the charge compensating and pH regulating voltage-gated proton channel (H1). The data suggests that human PMN and the PLB 985 generate ROS via a general mechanism, consistent of NOX2 and H1. Additionally, we advanced a mathematical model based on the biophysical properties of NOX2 and H1. Our results strongly suggest the essential interconnection of H1 and NOX2 during the respiratory burst of phagocytes. Zinc chelation during the time course of the experiments postulates that zinc leads to an irreversible termination of the respiratory burst over time. Flow cytometry shows cell death triggered by high zinc concentrations and PMA. Our data might help to elucidate the complex interaction of proteins during the respiratory burst and contribute to decipher its termination.

摘要

吞噬细胞的呼吸爆发对人类的生存至关重要。先天免疫防御依赖于 NADPH 氧化酶 (NOX2) 产生的活性氧 (ROS)。ROS 可以杀死病原体,同时通过 NOX2 将电子穿过质膜转移会使细胞去极化。同时,质子被释放到细胞质中。在这里,我们将新鲜分离的人多形核白细胞 (PMN) 与粒细胞样细胞系 PLB 985 进行比较。我们在抑制电荷补偿和 pH 调节电压门控质子通道 (H1) 的同时记录 ROS 的产生。数据表明,人类 PMN 和 PLB 985 通过包含 NOX2 和 H1 的通用机制产生 ROS。此外,我们基于 NOX2 和 H1 的生物物理特性提出了一个数学模型。我们的结果强烈表明,在吞噬细胞的呼吸爆发过程中,H1 和 NOX2 之间存在着必不可少的联系。实验过程中的锌螯合作用表明,锌会导致呼吸爆发随着时间的推移而不可逆地终止。流式细胞术显示高锌浓度和 PMA 触发的细胞死亡。我们的数据可能有助于阐明呼吸爆发过程中蛋白质的复杂相互作用,并有助于揭示其终止机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/d4504e00b7e6/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/2e6b6d400235/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/3fcef0be9b2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/fe6c49c6fd85/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/97b9da1aff11/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/c98536a4acbc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/a925ab19e5e4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/1ef7722d5cbf/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/cc95522fb11b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/c4030f1e4c25/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/68c41e5aefe7/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/1ed5f3196f59/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/54be08b70622/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/674c82125dde/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/0ee4279b2b40/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/d4504e00b7e6/mmcfigs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/2e6b6d400235/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/3fcef0be9b2e/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/fe6c49c6fd85/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/97b9da1aff11/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/c98536a4acbc/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/a925ab19e5e4/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/1ef7722d5cbf/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/cc95522fb11b/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/c4030f1e4c25/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/68c41e5aefe7/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/1ed5f3196f59/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/54be08b70622/mmcfigs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/674c82125dde/mmcfigs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/0ee4279b2b40/mmcfigs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/861c/8476447/d4504e00b7e6/mmcfigs5.jpg

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