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创伤性脑损伤后中性粒细胞的快速有序迁移依赖于 MMP9/13。

Rapid orderly migration of neutrophils after traumatic brain injury depends on MMP9/13.

机构信息

Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing, 400715, PR China.

Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, PR China.

出版信息

Biochem Biophys Res Commun. 2021 Nov 19;579:161-167. doi: 10.1016/j.bbrc.2021.09.044. Epub 2021 Sep 22.

Abstract

Macrophages and granulocytes play an important role in various injuries and post-traumatic repair. Due to the limited number of neutrophils in the brain, their role in traumatic brain injury has rarely been mentioned. Here, neutrophils were found to take over the role of macrophages after brain injury in the absence of macrophages. Neutrophils have the characteristics of long residence time and number advantage to actively remove the apoptotic debris. The number of neutrophils recruited was effectively reduced by inhibiting IL-1β. Interestingly, neutrophils migrated regularly and rapidly to the wound during the early stages of brain injury through three paths. They first infiltrated the wound mainly through blood circulation around the eyes, then became unscrupulous and began to move directly across the brain. In addition, MMP9 and MMP13 were found to be related to the migration of neutrophils, and inhibition of MMP could significantly inhibit the number and speed of neutrophils' migration. Our study showed that neutrophils rely on MMP9 and MMP13 for a rapid and orderly response to brain injury to maintain central nervous system stability in the absence or decrease of macrophages.

摘要

巨噬细胞和粒细胞在各种损伤和创伤后修复中发挥着重要作用。由于脑中中性粒细胞数量有限,其在创伤性脑损伤中的作用很少被提及。在这里,在没有巨噬细胞的情况下,研究发现在脑损伤后中性粒细胞会接管巨噬细胞的作用。中性粒细胞具有居留时间长和数量优势的特点,可以主动清除凋亡的碎片。通过抑制白细胞介素-1β(IL-1β),可有效减少募集的中性粒细胞数量。有趣的是,中性粒细胞通过三种途径在脑损伤早期有规律地、快速地迁移到伤口处。它们首先主要通过眼周血液循环浸润到伤口处,然后变得肆无忌惮,开始直接穿过大脑移动。此外,还发现 MMP9 和 MMP13 与中性粒细胞的迁移有关,抑制 MMP 可显著抑制中性粒细胞迁移的数量和速度。我们的研究表明,中性粒细胞依赖 MMP9 和 MMP13 来快速、有序地对脑损伤做出反应,在巨噬细胞缺失或减少的情况下维持中枢神经系统的稳定。

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