Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues.
Crosstalk Between CD11b and Piezo1 Mediates Macrophage Responses to Mechanical Cues.
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DOI：
10.3389/fimmu.2021.689397
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发表时间：
2021
影响因子：
7.3
通讯作者：
Liu WF
中科院分区：
文献类型：
--
作者：
Atcha H;Meli VS;Davis CT;Brumm KT;Anis S;Chin J;Jiang K;Pathak MM;Liu WF
巨噬细胞是先天免疫系统的多功能细胞，通过响应微环境的动态变化来发挥多种功能。虽然包括细胞因子和趋化因子在内的可溶性信号的作用已被广泛研究，但包括机械刺激在内的物理信号在调节巨噬细胞形态和功能方面的作用尚不清楚。在这项研究中，我们研究了静态和循环单轴拉伸对巨噬细胞炎症和愈合激活的影响。我们发现循环拉伸改变了巨噬细胞形态和对IFNγ/LPS和IL4/IL13的反应。有趣的是，我们发现静态和循环拉伸都抑制IFNγ/LPS诱导的炎症。相比之下，IL4/IL13介导的愈合反应在循环拉伸条件下受到抑制，但在静态拉伸条件下得到增强。在机制上，静态和循环拉伸都增加了整合素CD11b （αM整合素）的表达，降低了机械敏感离子通道Piezo1的表达，并且通过siRNA敲低CD11b或Piezo1都消除了拉伸介导的炎症反应变化。此外，我们发现CD11b的敲低增强了Piezo1的表达，反之，Piezo1的敲低增强了CD11b的表达，这表明整合素和离子通道之间可能存在串扰。最后，拉伸介导的巨噬细胞活化差异也依赖于肌动蛋白，因为肌动蛋白聚合的药理抑制消除了拉伸引起的活化变化。总之，本研究表明，物理环境与生化信号协同调节巨噬细胞的形态和功能，并提示CD11b和Piezo1串扰在巨噬细胞的机械转导中起作用。
Macrophages are versatile cells of the innate immune system that perform diverse functions by responding to dynamic changes in their microenvironment. While the effects of soluble cues, including cytokines and chemokines, have been widely studied, the effects of physical cues, including mechanical stimuli, in regulating macrophage form and function are less well understood. In this study, we examined the effects of static and cyclic uniaxial stretch on macrophage inflammatory and healing activation. We found that cyclic stretch altered macrophage morphology and responses to IFNγ/LPS and IL4/IL13. Interestingly, we found that both static and cyclic stretch suppressed IFNγ/LPS induced inflammation. In contrast, IL4/IL13 mediated healing responses were suppressed with cyclic but enhanced with static stretch conditions. Mechanistically, both static and cyclic stretch increased expression of the integrin CD11b (αM integrin), decreased expression of the mechanosensitive ion channel Piezo1, and knock down of either CD11b or Piezo1 through siRNA abrogated stretch-mediated changes in inflammatory responses. Moreover, we found that knock down of CD11b enhanced the expression of Piezo1, and conversely knock down of Piezo1 enhanced CD11b expression, suggesting the potential for crosstalk between integrins and ion channels. Finally, stretch-mediated differences in macrophage activation were also dependent on actin, since pharmacological inhibition of actin polymerization abrogated the changes in activation with stretch. Together, this study demonstrates that the physical environment synergizes with biochemical cues to regulate macrophage morphology and function, and suggests a role for CD11b and Piezo1 crosstalk in mechanotransduction in macrophages.
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影响因子：
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