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論文
- タイトル
- タイトル（英）
- UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis.
- 参照URL
- https://researchmap.jp/read0091842/published_papers/24701233
- 著者
- 著者（英）
- Schuichi Koizumi,Yukari Shigemoto-Mogami,Kaoru Nasu-Tada,Yoichi Shinozaki,Keiko Ohsawa,Makoto Tsuda,Bhalchandra V Joshi,Kenneth A Jacobson,Shinichi Kohsaka,Kazuhide Inoue
- 担当区分
- 概要
- 概要（英）
- Microglia, brain immune cells, engage in the clearance of dead cells or dangerous debris, which is crucial to the maintenance of brain functions. When a neighbouring cell is injured, microglia move rapidly towards it or extend a process to engulf the injured cell. Because cells release or leak ATP when they are stimulated or injured, extracellular nucleotides are thought to be involved in these events. In fact, ATP triggers a dynamic change in the motility of microglia in vitro and in vivo, a previously unrecognized mechanism underlying microglial chemotaxis; in contrast, microglial phagocytosis has received only limited attention. Here we show that microglia express the metabotropic P2Y6 receptor whose activation by endogenous agonist UDP triggers microglial phagocytosis. UDP facilitated the uptake of microspheres in a P2Y6-receptor-dependent manner, which was mimicked by the leakage of endogenous UDP when hippocampal neurons were damaged by kainic acid in vivo and in vitro. In addition, systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in messenger RNA encoding P2Y6 receptors that colocalized with activated microglia were observed. Thus, the P2Y6 receptor is upregulated when neurons are damaged, and could function as a sensor for phagocytosis by sensing diffusible UDP signals, which is a previously unknown pathophysiological function of P2 receptors in microglia.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature
- 巻
- 446
- 号
- 7139
- 開始ページ
- 1091
- 終了ページ
- 5
- 出版年月
- 2007年4月26日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- 共同研究・競争的資金等の研究課題
研究者
篠﨑 陽一
(シノザキ ヨウイチ)