Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway
Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway
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DOI：
10.1172/jci7451
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发表时间：
1999-12-01
影响因子：
15.9
通讯作者：
Coffman, TM
中科院分区：
文献类型：
--
作者：
Nataraj, C;Oliverio, MI;Coffman, TM
肾素-血管紧张素系统(RAS)是血管张力和血压的关键调节因子。此外，血管紧张素II还具有多种细胞效应，可能与疾病的发病机制有关。利用缺乏血管紧张素II AT(1A)受体的Agtr1a(-/-)小鼠，我们鉴定了RAS调节免疫系统的新功能。我们发现，血管紧张素II通过免疫细胞上的1型(AT(1))受体作用，触发脾淋巴细胞的增殖。这些行动有助于增强细胞同种免疫反应的活力。在淋巴器官中，存在足够的RAS成分，以在免疫反应期间激活AT(1)受体，促进细胞生长。这些作用需要钙调神经磷酸酶的激活。在心脏移植的活体模型中，AT(1)信号的缺失加重了钙调神经磷酸酶抑制剂环孢素A的免疫抑制作用。我们得出结论，抑制AT(1)受体信号转导作为一种抗炎和免疫抑制治疗应该是有用的。此外，RAS促进淋巴细胞活化的作用可能导致炎症，这种炎症是心脏和血管系统的一些疾病的特征。
The renin-angiotensin system (RAS) is a key regulator of vascular tone and blood pressure. In addition, angiotensin II also has a number of cellular effects that may contribute to disease pathogenesis. Using Agtr1a(-/-) mice, which lack AT(1A) receptors for angiotensin II, we have identified a novel function of the RAS to modulate the immune system. We find that angiotensin II, acting through type 1 (AT(1)) receptors on immune cells, triggers the proliferation of splenic lymphocytes. These actions contribute to the vigor of cellular alloimmune responses. Within lymphoid organs, sufficient components of the RAS are present to activate AT(1) receptors during an immune response, promoting cell growth. These actions require activation of calcineurin phosphatase. In an in vivo model of cardiac transplantation, the absence of AT(1) signaling accentuates the immunosuppressive effects of the calcineurin inhibitor cyclosporine. We conclude that inhibition of AT(1) receptor signaling should be useful as an anti-inflammatory and immunosuppressive therapy. Furthermore, the actions of the RAS to promote lymphocyte activation may contribute to inflammation that characterizes a number of diseases of the heart and the vascular system.