Phospholipid localization implies microglial morphology and function via Cdc42 in vitro
Phospholipid localization implies microglial morphology and function via Cdc42 in vitro
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DOI：
10.1002/glia.23123
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发表时间：
2017-05-01
期刊：
影响因子：
6.2
通讯作者：
Kiyama, Hiroshi
中科院分区：
文献类型：
--
作者：
Tokizane, Kyohei;Konishi, Hiroyuki;Kiyama, Hiroshi
在静止状态下，小胶质细胞呈现分枝状，而不是损伤或炎症后的变形虫样形态。小胶质细胞的体外形态学调控还不是很成功，这阻碍了小胶质细胞研究的进展。我们证明，溶血磷脂酰丝氨酸（LysoPS），一种溶血磷脂，迅速和实质性地改变了原代培养的小胶质细胞的形态，在体内类似的分枝的形状在受体的独立方式。该机制由Cdc 42活性介导。LysoPS掺入质膜并通过Lands循环转化为磷脂酰丝氨酸（PS）。膜上积累的PS募集Cdc 42。Cdc 42和PS共定位主要在初级和次级过程中，但不是在外周分支或提示的小胶质细胞。沿着形态学变化，LysoPS抑制炎性细胞因子产生和NF-κ B活性。本研究提供了一种工具，操纵一个小胶质细胞表型从一个变形虫到一个完全分歧在体外，这肯定有助于研究探索小胶质细胞的生理和病理。
Under a quiescent state, microglia exhibit a ramified shape, rather than the amoeboid-like morphology following injury or inflammation. The manipulation of microglial morphology in vitro has not been very successful, which has impeded the progress of microglial studies. We demonstrate that lysophosphatidylserine (LysoPS), a kind of lysophospholipids, rapidly and substantially alters the morphology of primary cultured microglia to an in vivo-like ramified shape in a receptor independent manner. This mechanism is mediated by Cdc42 activity. LysoPS is incorporated into the plasma membrane and converted to phosphatidylserine (PS) via the Lands' cycle. The accumulated PS on the membrane recruits Cdc42. Both Cdc42 and PS colocalize predominantly in primary and secondary processes, but not in peripheral branches or tips of microglia. Along with the morphological changes LysoPS suppresses inflammatory cytokine production and NF-kB activity. The present study provides a tool to manipulate a microglial phenotype from an amoeboid to a fully ramified in vitro, which certainly contributes to studies exploring microglial physiology and pathology.