Electrical and Computer Engineering Department, University of Houston, Houston, Texas; Texas Center for Superconductivity, University of Houston, Houston, Texas.
The Houston Methodist Research Institute, Houston, Texas; Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, China.
Biophys J. 2018 Apr 24;114(8):2001-2013. doi: 10.1016/j.bpj.2018.03.002.
Macrophages play a crucial role in homeostasis, regeneration, and innate and adaptive immune responses. Functionally different macrophages have different shapes and molecular phenotypes that depend on the actin cytoskeleton, which is regulated by the small GTPase RhoA. The naive M0 macrophages are slightly elongated, proinflammatory M1 are round, and M2 antiinflammatory macrophages are elongated. We have recently shown in the rodent model system that genetic or pharmacologic interference with the RhoA pathway deregulates the macrophage actin cytoskeleton, causes extreme macrophage elongation, and prevents macrophage migration. Here, we report that an exposure of macrophages to a nonuniform magnetic field causes extreme elongation of macrophages and has a profound effect on their molecular components and organelles. Using immunostaining and Western blotting, we observed that magnetic force rearranges the macrophage actin cytoskeleton, the Golgi complex, and the cation channel receptor TRPM2, and modifies the expression of macrophage molecular markers. We have found that the magnetic-field-induced alterations are very similar to changes caused by RhoA interference. We also analyzed magnetic-field-induced forces acting on macrophages and found that the location and alignment of magnetic-field-elongated macrophages correlate very well with the simulated distribution and orientation of such magnetic force lines.
巨噬细胞在维持内环境稳定、再生以及先天和适应性免疫反应中发挥着关键作用。功能不同的巨噬细胞具有不同的形状和分子表型，这取决于肌动蛋白细胞骨架，而肌动蛋白细胞骨架受 RhoA 小 GTPase 的调节。幼稚的 M0 巨噬细胞略微拉长，促炎的 M1 呈圆形，抗炎的 M2 巨噬细胞呈拉长状。我们最近在啮齿动物模型系统中表明，RhoA 通路的遗传或药理学干扰会使巨噬细胞的肌动蛋白细胞骨架失调，导致巨噬细胞极度拉长，并阻止巨噬细胞迁移。在这里，我们报告说，巨噬细胞暴露于非均匀磁场会导致巨噬细胞极度伸长，并对其分子成分和细胞器产生深远影响。通过免疫染色和 Western blot，我们观察到磁力重新排列了巨噬细胞的肌动蛋白细胞骨架、高尔基体和阳离子通道受体 TRPM2，并改变了巨噬细胞分子标志物的表达。我们发现，磁场诱导的变化与 RhoA 干扰引起的变化非常相似。我们还分析了作用于巨噬细胞的磁场诱导力，发现磁场诱导伸长的巨噬细胞的位置和排列与模拟的这种磁力线的分布和方向非常吻合。
