Mechanical deformation induces depolarization of neutrophils.
Mechanical deformation induces depolarization of neutrophils.
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DOI：
10.1126/sciadv.1602536
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发表时间：
2017-06
期刊：
影响因子：
13.6
通讯作者：
Chilvers ER
中科院分区：
文献类型：
--
作者：
Ekpenyong AE;Toepfner N;Fiddler C;Herbig M;Li W;Cojoc G;Summers C;Guck J;Chilvers ER
在体内模拟机械变形快速去肺纤维化-一种在急性肺损伤中可能失败的机制。中性粒细胞从静息状态到致敏状态的转变是其作为有能力的免疫细胞发挥功能的基本要求。这种转变不仅可以由化学信号引起，也可以由机械扰动引起。任何一个停止后，这些细胞逐渐恢复到静止状态超过40至120分钟。我们使用两个生物物理工具，光学担架和一种新的微循环模拟，影响生理相关的机械变形的单个非粘附的人中性粒细胞。我们建立了定量形态学分析和机械表型作为中性粒细胞启动的无标记标记物。我们表明，持续的机械变形的启动细胞可以引起主动去极化，发生两个数量级的速度比自发剥夺。这项工作提供了一个细胞水平的机制，可能解释最近的临床研究表明，潜在的重要性，和生理作用，中性粒细胞剥夺在体内和病理生理意义时，这种失活受损，特别是在疾病，如急性肺损伤。
In vivo–mimicking mechanical deformations quickly depolarize neutrophils—a mechanism potentially failing in acute lung injury. The transition of neutrophils from a resting state to a primed state is an essential requirement for their function as competent immune cells. This transition can be caused not only by chemical signals but also by mechanical perturbation. After cessation of either, these cells gradually revert to a quiescent state over 40 to 120 min. We use two biophysical tools, an optical stretcher and a novel microcirculation mimetic, to effect physiologically relevant mechanical deformations of single nonadherent human neutrophils. We establish quantitative morphological analysis and mechanical phenotyping as label-free markers of neutrophil priming. We show that continued mechanical deformation of primed cells can cause active depolarization, which occurs two orders of magnitude faster than by spontaneous depriming. This work provides a cellular-level mechanism that potentially explains recent clinical studies demonstrating the potential importance, and physiological role, of neutrophil depriming in vivo and the pathophysiological implications when this deactivation is impaired, especially in disorders such as acute lung injury.