Aged neutrophils contribute to the first line of defense in the acute inflammatory response
Aged neutrophils contribute to the first line of defense in the acute inflammatory response
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DOI：
10.1182/blood-2016-05-718999
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发表时间：
2016-11-10
期刊：
影响因子：
20.3
通讯作者：
Reichel, Christoph A.
中科院分区：
文献类型：
--
作者：
Uhl, Bernd;Vadlau, Yannick;Reichel, Christoph A.
在稳态条件下，老化的中性粒细胞从骨髓、肝脏和脾脏的循环中去除，从而维持骨髓细胞的稳态。然而，这些老化的免疫细胞在炎症条件下的命运在很大程度上仍然不清楚。在这里，我们证明，在急性炎症反应期间内毒素血症，老年中性粒细胞停止返回骨髓，而是迅速迁移到炎症部位。到达炎症组织后，发现老化中性粒细胞与随后招募的非老化中性粒细胞相比表现出更高的吞噬活性。在炎症条件下，老年中性粒细胞的这种独特行为取决于其分子库中特定的年龄相关变化，这些分子库使这些“有经验的”免疫细胞能够立即将炎症信号转化为免疫反应。特别是，老年中性粒细胞参与Toll样受体-4和p38 MAPK依赖性途径，诱导β 2整联蛋白的构象变化，使这些吞噬细胞有效地完成其在炎症反应前线的使命。因此，循环中的衰老可能代表了中性粒细胞的一个关键过程，使这些免疫细胞能够正确地发挥其功能特性，用于宿主防御。
Under steady-state conditions, aged neutrophils are removed from the circulation in bone marrow, liver, and spleen, thereby maintaining myeloid cell homeostasis. The fate of these aged immune cells under inflammatory conditions, however, remains largely obscure. Here, we demonstrate that in the acute inflammatory response during endotoxemia, aged neutrophils cease returning to the bone marrow and instead rapidly migrate to the site of inflammation. Having arrived in inflamed tissue, aged neutrophils were found to exhibit a higherphagocytic activity as compared with the subsequently recruited nonaged neutrophils. This distinct behavior of aged neutrophils under inflammatory conditions is dependent on specific age-related changes in their molecular repertoire that enable these "experienced" immune cells to instantly translate inflammatory signals into immune responses. In particular, aged neutrophils engage Toll-like receptor-4- and p38 MAPK-dependent pathways to induce conformational changes in beta 2 integrins that allow these phagocytes to effectively accomplish their mission in the front line of the inflammatory response. Hence, ageing in the circulation might represent a critical process for neutrophils that enables these immune cells to properly unfold their functional properties for host defense.