...
首页> 外文期刊>Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism >Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke
【24h】

Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke

机译:从活化的中性粒细胞释放的精氨酸酶I在中风的鼠模型中诱导外周免疫抑制

获取原文
获取原文并翻译 | 示例
           

摘要

Transient suppression of peripheral immunity is a major source of complication for patients suffering from ischemic stroke. The release of Arginase I (ArgI) from activated neutrophils has recently been associated with T-cell dysfunction in a number of pathologies. However, this pathway has not been previously explored in ischemic stroke. Using the murine model of transient middle cerebral artery occlusion, we explored effects of stroke on peripheral T-cell function and evaluated the role of neutrophils and ArgI. Stimulation of splenic T cells from post-stroke animals with anti-CD3/CD28 resulted in decreased proliferation and interferon-gamma production when compared with sham-surgery controls. Flow cytometric analysis of intrasplenic leukocytes exposed the presence of a transient population of activated neutrophils that correlated quantitatively with elevated ArgI levels in culture media. In vitro activation of purified resting neutrophils from unmanipulated controls confirmed the capacity for murine neutrophils to release ArgI from preformed granules. We observed decreased expression of the L-arg-sensitive CD3 zeta on T cells, consistent with decreased functional activity. Critically, L-arg supplementation restored the functional response of post-stroke T cells to mitogenic stimulation. Together, these data outline a novel mechanism of reversible, neutrophil-mediated peripheral immunosuppression related to ArgI release following ischemic stroke.
机译:对于患有缺血性中风的患者,短暂抑制外周免疫是并发症的主要来源。从活化的嗜中性粒细胞中释放出精氨酸酶I(ArgI)最近与许多病理学中的T细胞功能障碍有关。然而,该途径先前尚未在缺血性中风中探索。使用短暂脑中动脉阻塞的小鼠模型,我们探讨了中风对外周血T细胞功能的影响,并评估了中性粒细胞和ArgI的作用。与假手术对照组相比,用抗CD3 / CD28刺激中风后动物的脾脏T细胞导致增殖和干扰素-γ生成减少。脾内白细胞的流式细胞术分析揭示了活化嗜中性粒细胞的瞬时群体的存在,其与培养基中升高的ArgI水平定量相关。来自未经操作的对照的纯化静息嗜中性粒细胞的体外活化证实了鼠嗜中性粒细胞从预先形成的颗粒中释放ArgI的能力。我们观察到L-arg敏感的CD3 zeta在T细胞上的表达减少,与功能活性降低一致。至关重要的是,补充L-arg可恢复中风后T细胞对促有丝分裂刺激的功能反应。总之,这些数据概述了缺血性卒中后与ArgI释放相关的可逆性中性粒细胞介导的外周免疫抑制的新机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号