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流动状态下人类中性粒细胞对P-选择素的力依赖性钙信号传导及其途径

Force-dependent calcium signaling and its pathway of human neutrophils on P-selectin in flow.

作者信息

Huang Bing, Ling Yingchen, Lin Jiangguo, Du Xin, Fang Ying, Wu Jianhua

机构信息

School of Bioscience & Bioengineering, South China University of Technology, Guangzhou, 510006, China.

Hematology and Oncology Division, Guangdong General Hospital, Guangzhou, 510080, China.

出版信息

Protein Cell. 2017 Feb;8(2):103-113. doi: 10.1007/s13238-016-0364-4. Epub 2017 Jan 18.

DOI:10.1007/s13238-016-0364-4
PMID:28097631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5291781/
Abstract

P-selectin engagement of P-selectin glycoprotein ligand-1 (PSGL-1) causes circulating leukocytes to roll on and adhere to the vascular surface, and mediates intracellular calcium flux, a key but unclear event for subsequent arresting firmly at and migrating into the infection or injured tissue. Using a parallel plate flow chamber technique and intracellular calcium ion detector (Fluo-4 AM), the intracellular calcium flux of firmly adhered neutrophils on immobilized P-selectin in the absence of chemokines at various wall shear stresses was investigated here in real time by fluorescence microscopy. The results demonstrated that P-selectin engagement of PSGL-1 induced the intracellular calcium flux of firmly adhered neutrophils in flow, increasing P-selectin concentration enhanced cellular calcium signaling, and, force triggered, enhanced and quickened the cytoplasmic calcium bursting of neutrophils on immobilized P-selectin. This P-selectin-induced calcium signaling should come from intracellular calcium release rather than extracellular calcium influx, and be along the mechano-chemical signal pathway involving the cytoskeleton, moesin and Spleen tyrosine kinase (Syk). These results provide a novel insight into the mechano-chemical regulation mechanism for P-selectin-induced calcium signaling of neutrophils in flow.

摘要

P选择素与P选择素糖蛋白配体-1（PSGL-1）结合，使循环中的白细胞在血管表面滚动并黏附，介导细胞内钙流，这是随后在感染或损伤组织中牢固驻留并迁移的关键但尚不清楚的事件。利用平行板流动腔技术和细胞内钙离子探测器（Fluo-4 AM），通过荧光显微镜实时研究了在无趋化因子的情况下，不同壁面剪切应力下固定化P选择素上牢固黏附的中性粒细胞的细胞内钙流。结果表明，PSGL-1与P选择素结合可诱导流动中牢固黏附的中性粒细胞产生细胞内钙流，增加P选择素浓度可增强细胞钙信号，并且在力触发下，可增强并加速固定化P选择素上中性粒细胞的细胞质钙爆发。这种P选择素诱导的钙信号应来自细胞内钙释放而非细胞外钙内流，且是沿着涉及细胞骨架、埃兹蛋白和脾酪氨酸激酶（Syk）的机械化学信号通路产生的。这些结果为流动状态下P选择素诱导中性粒细胞钙信号的机械化学调节机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/4b59400862e5/13238_2016_364_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/803efc92f30d/13238_2016_364_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/8b6903f523bc/13238_2016_364_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/a387878541cb/13238_2016_364_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/6b9d156b95d9/13238_2016_364_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/4c4c48fe99e7/13238_2016_364_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/74ce836724b2/13238_2016_364_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/4b59400862e5/13238_2016_364_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/803efc92f30d/13238_2016_364_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/8b6903f523bc/13238_2016_364_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/a387878541cb/13238_2016_364_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/6b9d156b95d9/13238_2016_364_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/4c4c48fe99e7/13238_2016_364_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/74ce836724b2/13238_2016_364_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0c2/5291781/4b59400862e5/13238_2016_364_Fig7_HTML.jpg

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