Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation
Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation
复制标题
DOI：
10.1126/science.1195491
复制
发表时间：
2010-10-15
期刊：
影响因子：
56.9
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
--
作者：
McDonald, Braedon;Pittman, Keir;Kubes, Paul
中性粒细胞从血液中募集到无菌炎症部位，在那里它们有助于伤口愈合，但也可能导致组织损伤。通过使用旋转圆盘共聚焦活体显微镜，我们研究了中性粒细胞募集到体内局灶性肝坏死部位的动力学和分子机制。从坏死细胞释放的三磷酸腺苷激活Nlrp3炎性体以产生炎症微环境，其警告循环中性粒细胞粘附在肝窦内。随后，血管内趋化因子梯度的产生引导中性粒细胞通过健康组织向损伤灶迁移。最后，从坏死细胞释放的甲酰肽信号引导中性粒细胞通过非灌注的血窦进入损伤。因此，动态体内成像揭示了一个多步骤层次的定向线索，引导中性粒细胞定位到无菌炎症部位。
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.