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【进展|热点】SCIENCE:嗜中性粒细胞前来营救(ZT)

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嗜中性粒细胞是一种常见类型的血液白细胞,它不但会对微生物感染做出反应,而且它还会对由例如创伤或器官坏死所引起的无菌性损伤做出反应。

在 2010 年 10 月 15 日刊《科学》杂志中的一项研究中, McDonald 等人描述了应用体内动态成像技术来调查嗜中性粒细胞被损伤组织招募的基础机制。经过一个多步骤的级联分子反应事件(它以濒死细胞所释放的 ATP 作为开始,它还涉及到某驱化因子梯度及线粒体信号肽的形成),循环中的嗜中性粒细胞通过血管内渠道被快速地引导到损伤的部位。研究人员提出,这一级联反应已经进化成能够允许嗜中性粒细胞在通行的时候留在血管之中,因而限制了其对周边健康组织的附带损害。

<center> <strong>Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation</strong></center>

Braedon McDonald,1 Keir Pittman,1 Gustavo B. Menezes,1~undefined Simon A. Hirota,2 Ingrid Slaba,1 Christopher C. M. Waterhouse,1,3 Paul L. Beck,2,4 Daniel A. Muruve,1,4 Paul Kubes1,

Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage. By using spinning disk confocal intravital microscopy, we examined the kinetics and molecular mechanisms of neutrophil recruitment to sites of focal hepatic necrosis in vivo. Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids. Subsequently, generation of an intravascular chemokine gradient directed neutrophil migration through healthy tissue toward foci of damage. Lastly, formyl-peptide signals released from necrotic cells guided neutrophils through nonperfused sinusoids into the injury. Thus, dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation.

相关文献 http://www.sciencemag.org/cgi/content/short/330/6002/362

有关嗜中性粒细胞营救视频 http://video.sciencemag.org/VideoLab/635318282001/1

作者Paul Kubes 就为什么这些发现可导致能挫败过度炎症反应的不良效应的新药研发进行了讨论
相关采访音频 http://www.sciencemag.org/cgi/content/full/330/6002/362/DC2

FROM Science Roundup in Chinese
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