微血管血栓形成与 CD40/CD40L 信号通路。
Microvascular thrombosis and CD40/CD40L signaling.
机构信息
Wolfson Neuroscience Laboratories, Faculty of Medicine, Imperial College, London, UK.
出版信息
J Thromb Haemost. 2011 Mar;9(3):574-81. doi: 10.1111/j.1538-7836.2010.04176.x.
BACKGROUND
Although inflammation and thrombosis are now recognized to be interdependent processes that activate and perpetuate each other, the signaling molecules that link these two processes remain poorly understood.
OBJECTIVES
The objective of this study was to assess the contribution of the CD40/CD40L signaling system to the enhanced microvascular thrombosis that accompanies two distinct experimental models of inflammation, that is, endotoxemia (lipopolysaccharide [LPS]) and dextran sodium sulfate (DSS)-induced colitis.
METHODS
Thrombosis was induced in cerebral (LPS model) and cremaster muscle (DSS model) arterioles and venules of wild-type (WT) mice and mice deficient in either CD40 (CD40(-/-)) or CD40L (CD40L(-/-)), using the light/dye (photoactivation) method.
RESULTS AND CONCLUSIONS
A comparison of thrombus formation between WT and mutant mice revealed a role for CD40 and/or CD40L in the inflammation-enhanced thrombosis responses in both of the cerebral and muscle vasculatures. However, the relative contributions of CD40 and its ligand to thrombus formation differed between vascular beds (brain vs. muscle) and vessel types (arterioles vs. venules). The protective effect of CD40L deficiency in cerebral arterioles exposed to LPS was significantly blunted by administration of soluble CD40L. These findings implicate CD40 and its ligand in the enhanced thrombus formation that is associated with acute and chronic inflammation.
背景
虽然炎症和血栓形成现在被认为是相互依存的过程，它们相互激活和持续，但将这两个过程联系起来的信号分子仍知之甚少。
目的
本研究旨在评估 CD40/CD40L 信号系统对两种不同炎症模型（即内毒素血症（脂多糖[LPS]）和葡聚糖硫酸钠（DSS）诱导的结肠炎）伴随的增强微血管血栓形成的贡献。
方法
使用光/染料（光激活）法在野生型（WT）小鼠和缺乏 CD40（CD40(-/-)）或 CD40L（CD40L(-/-)）的小鼠的大脑（LPS 模型）和提睾肌（DSS 模型）小动脉和小静脉中诱导血栓形成。
结果和结论
WT 小鼠和突变小鼠之间的血栓形成比较表明，CD40 和/或 CD40L 在两种大脑和肌肉血管的炎症增强的血栓形成反应中起作用。然而，CD40 和其配体对血栓形成的相对贡献在血管床（大脑与肌肉）和血管类型（小动脉与小静脉）之间有所不同。在 LPS 暴露的大脑小动脉中，CD40L 缺乏的保护作用被可溶性 CD40L 显著削弱。这些发现表明 CD40 和其配体参与了与急性和慢性炎症相关的增强的血栓形成。
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