Extracellular acidification decreases the basal motility of cultured mouse microglia via the rearrangement of the actin cytoskeleton
Extracellular acidification decreases the basal motility of cultured mouse microglia via the rearrangement of the actin cytoskeleton
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DOI：
10.1016/s0006-8993(99)02221-0
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发表时间：
2000-01-17
期刊：
影响因子：
2.9
通讯作者：
Nolte, C
中科院分区：
文献类型：
--
作者：
Faff, L;Nolte, C
本研究旨在探讨细胞外pH（pH（0））对体外培养的小鼠小胶质细胞运动功能的影响。我们发现，通过计算机辅助视频检测，小胶质细胞的基础运动性在酸性环境中降低，但在碱性环境中不降低。胞外酸化影响F-肌动蛋白细胞骨架的结构，诱导肌动蛋白成束和应力纤维的形成。由pH（0）变化引起的细胞内pH（pH（i））变化似乎是运动性降低的先决条件，因为降低pH（i）的其他方法，即不含HCO的无Na+溶液和含尼日利亚菌素的溶液，模拟了细胞外酸化。与其对小胶质细胞基础运动性的显着影响相反，化学引诱物补体5a（C5 a）诱导的运动性增加不受酸性环境的影响。还在长期微趋化性测定中研究了pH与运动功能的关系，其中小胶质细胞在pH梯度内迁移。降低pH值至6.0或从测定培养基中去除Na+诱导的细胞内酸化降低了基底小胶质细胞的迁移。C5 a诱导的趋化性迁移被酸性环境适度降低。总之，我们的研究结果表明，酸化的小胶质细胞外环境导致pH值的降低（i），从而减少了基础的小胶质细胞的运动和C5 a诱导的趋化性通过重排的细胞骨架。因此，我们想推测，pHi的变化构成了一个重要的控制机制，在调节运动功能的小胶质细胞在文化中，也可能在完整的组织。(C)2000 Elsevier Science B. V. Au版权所有。
The present study was undertaken to examine the effect of extracellular pH (pH(0)) on the locomotor function of murine microglial cells in vitro. We have found that basal motility of microglia, as measured by a computer-assisted video assay, decreased in an acidic, but not in an alkaline environment. Extracellular acidification affected the architecture of F-actin cytoskeleton, inducing bundling of actin and the formation of stress fibers. The change in intracellular pH (pH(i)) resulting from the change in pH(0) seems to be a prerequisite for the motility decrease since other means to decrease pH(i), namely Na+-free solution tin the absence of HCO; and nigericin-containing solution, mimicked the extracellular acidification. In contrast to its pronounced effect on basal motility of microglial cells, the motility increase, as induced by the chemoattractant complement 5a (C5a), was not affected by the acidic environment. The relationship of pH, to the locomotor function was also studied in a long-term microchemotaxis assay where microglia migrated within a pH gradient. Intracellular acidification induced by lowering pH, to 6.0 or removal of Na+ from the assay medium decreased basal microglial cell migration. The C5a-induced chemotactic migration was moderately decreased by the acidic environment. In conclusion, our results suggest that acidification of the microglial extracellular milieu leads to a decrease in pH(i) and thereby reduces the basal microglial motility and C5a-induced chemotaxis via a rearrangement of the cytoskeleton. We would therefore Like to speculate that changes in pHi constitute an important control mechanism in regulating the locomotor function of microglia in culture and probably also in the intact tissue. (C) 2000 Elsevier Science B.V. AU rights reserved.