Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK.
Biotechnology Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307 Dresden, Germany.
Sci Adv. 2017 Jun 14;3(6):e1602536. doi: 10.1126/sciadv.1602536. eCollection 2017 Jun.
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.
中性粒细胞从静息状态向激活状态的转变是其作为功能完备的免疫细胞发挥作用的必要条件。这种转变不仅可以由化学信号触发，也可以由机械扰动引起。无论是哪种情况停止后，这些细胞在 40 到 120 分钟内逐渐恢复到静止状态。我们使用两种生物物理工具，即光镊和新型微循环模拟装置，对单个非黏附的人中性粒细胞进行生理相关的机械变形。我们建立了定量形态分析和力学表型作为中性粒细胞激活的无标记标志物。我们表明，持续的机械变形可以导致激活细胞的主动去极化，其发生速度比自发去激活快两个数量级。这项工作提供了一种细胞水平的机制，可能解释了最近的临床研究，这些研究表明中性粒细胞在体内去激活的潜在重要性和生理作用，以及当这种失活受损时的病理生理意义，特别是在急性肺损伤等疾病中。
