血管基底膜对中性粒细胞渗出的调节作用及其分子机制

批准号:
31970745
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
宋健
依托单位:
学科分类:
细胞外微环境与细胞间通讯
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
宋健
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中文摘要
中性粒细胞渗出是控制感染以及炎症性疾病的关键环节。血管内皮下基底膜是血管壁屏障的重要组成,影响白细胞的渗出和炎症反应的预后。由于基底膜结构难以在体外模拟,中性粒细胞穿过基底膜的过程及其调节机制尚不清楚。我们初步研究发现,内皮下腔内迁移和穿过基底膜是中性粒细胞穿过血管壁的限速步骤。在内皮下腔内迁移时,中性粒细胞通过β2整合素-ICAM1和α6β1整合素-层黏连蛋白,分别与血管内皮以及基底膜相互作用;当穿过基底膜时,中性粒细胞在细胞核周围形成F-肌动蛋白收缩环,收缩推动细胞核挤过基底膜。进入血管壁的中性粒细胞降低极化状态,下调钙离子信号和整合素受体的表面表达,提示血管壁屏障可能会影响中性粒细胞的生物学功能。本课题将进一步明确基底膜在中性粒细胞渗出中的作用,从显微影像的角度研究整合素信号对中性粒细胞运动和细胞骨架的调节基因及其上下游信号通路,为改善炎症治疗提供新思路,发现新靶点。
英文摘要
Neutrophil extravasation is a key step in the control of infections and inflammatory diseases. The endothelial basement membrane acts as an important vascular barrier, affecting the leukocyte extravasation and the prognosis of the inflammatory response. As the basement membrane structure is difficult to simulate in vitro, the process by which neutrophils penetrate the basement membrane and its regulatory mechanisms are unclear. Our preliminary study found that the process of neutrophils passing through the vascular wall are divided into three steps: crossing the endothelial layer, migrating in the abluminal space and penetrating the basement membrane, in which the abluminal migration and the penetration of the basement membrane are the rate-limiting steps. During the abluminal migration, neutrophils interact with the vascular endothelium and the basement membrane via β2 integrin-ICAM1 and α6β1 integrin-laminin respectively; When penetrating the basement membrane, an actin ring is formed around the nucleus, and the contraction pushes the nucleus through the basement membrane. Neutrophils entering the vessel wall reduce polarization and down-regulate calcium ion signaling as well as surface expression of integrin receptors. We assume that the barriers within the vessel wall may affect the biological function of neutrophils. This project will further clarify the role of the basement membrane in neutrophil extravasation, and study the regulation of integrin signaling on neutrophil motility and cytoskeleton as well as its signaling pathways, from the perspective of microscopic imaging, which may confer novel ideas and targets to the clinical treatment.
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DOI:10.3389/fonc.2021.731896
发表时间:2021
期刊:Frontiers in oncology
影响因子:4.7
作者:Yang F;Zhao J;Luo X;Li T;Wang Z;Wei Q;Lu H;Meng Y;Cai K;Lu L;Lu Y;Chen L;Sooranna SR;Luo L;Song J;Meng L
通讯作者:Meng L
DOI:10.3389/fimmu.2022.907599
发表时间:2022
期刊:FRONTIERS IN IMMUNOLOGY
影响因子:7.3
作者:Meng, Lingzhang;Chen, Shengcai;Shi, Guiling;He, Siyuan;Wang, Zechen;Shen, Jiajia;Wang, Jiajia;Sooranna, Suren Rao;Zhao, Jingjie;Song, Jian
通讯作者:Song, Jian
DOI:10.3389/fonc.2021.757641
发表时间:2021
期刊:Frontiers in oncology
影响因子:4.7
作者:Wang J;Huang M;Huang P;Zhao J;Tan J;Huang F;Ma R;Xiao Y;Deng G;Wei L;Wei Q;Wang Z;He S;Shen J;Sooranna S;Meng L;Song J
通讯作者:Song J
DOI:10.3389/fcell.2021.735307
发表时间:2021
期刊:Frontiers in cell and developmental biology
影响因子:5.5
作者:Meng L;Qin H;Zhao J;He S;Wei Q;Wang Z;Shen J;Sooranna S;Song J
通讯作者:Song J
DOI:10.1155/2021/5598627
发表时间:2021
期刊:Journal of immunology research
影响因子:4.1
作者:Meng Y;Cai K;Zhao J;Huang K;Ma X;Song J;Liu Y
通讯作者:Liu Y
国内基金
海外基金
