Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage
Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage
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DOI：
10.1124/jpet.105.086553
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发表时间：
2005-08-01
影响因子：
3.5
通讯作者：
Papapetropoulos, A
中科院分区：
文献类型：
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作者：
Roviezzo, F;Tsigkos, S;Papapetropoulos, A
血管生成素（Angs）是内皮选择性配体，其大部分作用通过Tie-2受体发挥。人们普遍认为，Ang-1促进血管结构的完整性，并表现出抗炎特性。相比之下，Ang-2的作用仍然不太清楚，因为它已被证明在不同的实验条件下表现为Tie-2激动剂或拮抗剂。为了确定Ang-2在急性炎症中的作用，我们研究了体内重组Ang-2给药的作用。我们在此表明，Ang-2，而不是Ang-1，以剂量依赖性方式诱导小鼠爪水肿形成;水肿似乎是快速达到峰值（在30分钟时最大），并在4小时内消退。Ang-2的作用通过与可溶形式的Tie-2受体或Ang-1共同施用而被阻断。NO和前列腺素E-2在小鼠爪注射后的水平保持不变，表明Ang-2的作用不涉及这些介质。此外，Ang-2对小鼠爪中的白细胞迁移具有弱刺激作用。同样，血管紧张素-2注入小鼠气囊产生的细胞外渗，在30分钟达到峰值只有适度的影响。然而，当细胞迁移引起酵母多糖，血管紧张素-2显着抑制白细胞迁移。我们的结论是，Ang-2本身刺激细胞贫乏的液体外渗，但在持续炎症的存在下，它减少了组织中的细胞浸润。
Angiopoietins (Angs) are endothelium-selective ligands that exert most of their actions through the Tie-2 receptor. It is widely accepted that Ang-1 promotes the structural integrity of blood vessels and exhibits anti-inflammatory properties. In contrast, the role of Ang-2 remains less clear because it has been shown to behave as a Tie-2 agonist or antagonist under different experimental conditions. To define the role of Ang-2 in acute inflammation, we studied the effects of recombinant Ang-2 administration in vivo. We show herein that Ang-2, but not Ang-1, induces edema formation in the mouse paw in a dose-dependent manner; the edema seems to be fast-peaking (maximum at 30 min) and resolves within 4 h. The effect of Ang-2 is blocked by the coadministration with a soluble form of the Tie-2 receptor or Ang-1. NO and prostaglandin E-2 levels in mouse paw following the injection of Ang-2 remained unaltered, suggesting that the action of Ang-2 does not involve these mediators. In addition, Ang-2 exerted a weak stimulatory effect on leukocyte migration in the mouse paw. Similarly, Ang-2 injected into the mouse air pouch produced only a modest effect on cell extravasation that peaked at 30 min. However, when cell migration was elicited using zymosan, Ang-2 significantly inhibited leukocyte migration. We conclude that Ang-2 by itself stimulates the extravasation of cell-poor fluid, but in the presence of ongoing inflammation it reduces cellular infiltration in tissues.