Tissue damage detection by osmotic surveillance
Tissue damage detection by osmotic surveillance
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DOI：
10.1038/ncb2818
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发表时间：
2013-09-01
影响因子：
21.3
通讯作者：
Niethammer, Philipp
中科院分区：
文献类型：
--
作者：
Enyedi, Balazs;Kala, Snigdha;Niethammer, Philipp
组织损伤是如何被检测到以诱导炎症反应的尚不清楚。大多数研究都集中在细胞破裂和坏死释放的损伤信号（1）。组织是否使用除了细胞溶解之外的其他线索来检测它们是否受损尚不清楚。我们发现，间质液和外部环境之间的渗透压差异介导的快速白细胞招聘的组织损伤部位在斑马鱼的细胞溶质磷脂酶a2（cPLA2）在损伤部位。cPLA2启动通过5-氧代-ETE受体（OXE-R）介导白细胞趋化性的非典型花生四烯酸代谢物的产生。因此，组织可以通过直接监测屏障完整性来检测损伤，细胞肿胀可能在该过程中起促炎中间体的作用。
How tissue damage is detected to induce inflammatory responses is unclear. Most studies have focused on damage signals released by cell breakage and necrosis(1). Whether tissues use other cues in addition to cell lysis to detect that they are damaged is unknown. We find that osmolarity differences between interstitial fluid and the external environment mediate rapid leukocyte recruitment to sites of tissue damage in zebrafish by activating cytosolic phospholipase a2 (cPLA2) at injury sites. cPLA2 initiates the production of non-canonical arachidonate metabolites that mediate leukocyte chemotaxis through a 5-oxo-ETE receptor (OXE-R). Thus, tissues can detect damage through direct surveillance of barrier integrity, with cell swelling probably functioning as a pro-inflammatory intermediate in the process.