Expression and function of lysophosphatidic acid receptors in cultured rodent microglial cells
Expression and function of lysophosphatidic acid receptors in cultured rodent microglial cells
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DOI：
10.1074/jbc.m102691200
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发表时间：
2001-07-13
影响因子：
4.8
通讯作者：
Ransom, BR
中科院分区：
文献类型：
--
作者：
Möller, T;Contos, JJ;Ransom, BR
小胶质细胞是中枢神经系统的常驻组织巨噬细胞。它们被各种侮辱迅速激活;最近，与细胞质Ca 2+信号相关的受体已被牵连在此类事件中。一类潜在的受体是识别溶血磷脂酸（LPA）的受体。LPA是一种磷脂信号分子，已显示可引起多种细胞反应，包括细胞质钙增加。我们研究了是否有任何已知的LPA受体基因（lp（A1）/Edg 2，lp（A2）/Edg 4，和lp（A3）/Edg 7）表达培养的小鼠或大鼠小胶质细胞。逆转录-聚合酶链反应表明，小鼠小胶质细胞主要表达的IP，基因，而大鼠小胶质细胞主要表达IP，虽然LPA诱导的细胞质Ca 2+浓度在两个小胶质细胞制剂的增加，反应有很大不同。大鼠小胶质细胞中的Ca 2+信号主要通过质膜的Ca 2+内流发生，而小鼠小胶质细胞中的Ca 2+信号是由于从细胞内储存释放。只有在高浓度下才招募额外的流入成分。此外，LPA还可诱导小鼠（而非大鼠）小胶质细胞代谢活性增加。我们的研究结果为小胶质细胞上LPA受体的功能提供了证据，因此，LPA可能在中枢神经系统损伤时作为小胶质细胞活化的介导剂发挥重要作用。
Microglia are the resident tissue macrophages of the central nervous system. They are rapidly activated by a variety of insults; and recently, receptors linked to cytoplasmic Ca2+ signals have been implicated in such events. One potential class of receptors are those recognizing lysophosphatidic acid (LPA). LPA is a phospholipid signaling molecule that has been shown to cause multiple cellular responses, including increases in cytoplasmic calcium. We examined whether any of the known LPA receptor genes (lp(A1)/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7) are expressed by cultured mouse or rat microglia. Reverse transcriptase-polymerase chain reaction indicated that mouse microglia predominantly expressed the Ip,, gene, whereas rat microglia predominantly expressed Ip,, Although LPA induced increases in the cytoplasmic Ca2+ concentration in both microglial preparations, the responses differed substantially. The Ca2+ signal in rat microglia occurred primarily through Ca2+ influx via the plasma membrane, whereas the Ca2+ signal in mouse microglia was due to release from intracellular stores. Only at high concentrations was an additional influx component recruited. Additionally, LPA induced increased metabolic activity in mouse (but not rat) microglial cells, Our findings provide evidence for functional LPA receptors on microglia, Thus, LPA might play an important role as a mediator of microglial activation in response to central nervous system injury.