Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
Neutrophil priming occurs in a sequential manner and can be visualized in living animals by monitoring IL-1β promoter activation.
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DOI：
10.4049/jimmunol.1402018
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发表时间：
2015-02-01
期刊：
影响因子：
--
通讯作者：
Takashima A
中科院分区：
文献类型：
--
作者：
Yao Y;Matsushima H;Ohtola JA;Geng S;Lu R;Takashima A
吞噬细胞功能的快速增强是中性粒细胞启动的标志。 GeneChip 分析揭示了从炎症部位分离的中性粒细胞的 CD54、dectin-2 和 IL-1β mRNA 表达升高。事实上，在从皮肤、腹膜和肺部炎症病变中回收的中性粒细胞中检测到了 CD54 和 dectin-2 蛋白表达，但在骨髓或外周血中未检测到。中性粒细胞在博伊登室迁移期间升高 CD54 和 dectin-2 mRNA，并在随后暴露于 GM-CSF 后获得 CD54 和 dectin-2 表面表达。从 IL-1β 启动子驱动的 DsRed 转基因小鼠中纯化的中性粒细胞在细胞迁移或暴露于 GM-CSF 期间获得了 DsRed 信号。在添加 GM-CSF 的培养物中，DsRed+（而非 DsRed-）中性粒细胞表达 CD54 和 dectin-2，并且从炎症部位回收的中性粒细胞表现出强烈的 DsRed 信号。然后通过在共聚焦显微镜下监测 DsRed 表达来研究化学诱导的炎症性皮肤损伤中中性粒细胞启动的动态过程。大多数 (>80%) Ly6G+ 中性粒细胞表达 DsRed，并且与 DsRed-/Ly6G+ 细胞相比，这些 DsRed+/Ly6G+ 细胞表现出更高速度的爬行运动。这是第一份显示活体动物中已启动的中性粒细胞运动行为的报告。我们认为中性粒细胞启动以连续方式发生，吞噬细胞功能快速增强，随后 CD54 和 dectin-2 mRNA 和蛋白表达、IL-1β 启动子激活和加速运动。这些发现不仅为我们理解中性粒细胞启动过程提供了新的概念框架，而且还揭示了许多以中性粒细胞浸润为特征的炎症性疾病的病理生理学的新见解。
Rapid enhancement of phagocyte functionality is a hallmark of neutrophil priming. GeneChip analyses unveiled elevated CD54, dectin-2, and IL-1β mRNA expression by neutrophils isolated from inflammatory sites. In fact, CD54 and dectin-2 protein expression was detected on neutrophils recovered from skin, peritoneal and lung inflammation lesions, but not on those in bone marrow or peripheral blood. Neutrophils elevated CD54 and dectin-2 mRNA during migration in Boyden chambers and acquired CD54 and dectin-2 surface expression after subsequent exposure to GM-CSF. Neutrophils purified from IL-1β promoter-driven DsRed transgenic mice acquired DsRed signals during cell migration or exposure to GM-CSF. CD54 and dectin-2 were expressed by DsRed+ (but not DsRed–) neutrophils in GM-CSF-supplemented culture, and neutrophils recovered from inflammatory sites exhibited strong DsRed signals. The dynamic process of neutrophil priming was then studied in chemically induced inflammatory skin lesions by monitoring DsRed expression under confocal microscopy. A majority (>80%) of Ly6G+ neutrophils expressed DsRed, and those DsRed+/Ly6G+ cells exhibited crawling motion with a higher velocity compared to the DsRed–/Ly6G+ counterpart. This is the first report showing motile behaviors of primed neutrophils in living animals. We propose that neutrophil priming occurs in a sequential manner with rapid enhancement of phagocyte functionality followed by CD54 and dectin-2 mRNA and protein expression, IL-1β promoter activation, and accelerated motility. Not only do these findings provide a new conceptual framework for our understanding of the process of neutrophil priming, they also unveil new insights into the pathophysiology of many inflammatory disorders characterized by neutrophil infiltration.
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影响因子：
5.5
作者：
Boxio, R;Bossenmeyer-Pourié, C;Nüsse, O
通讯作者：
Nüsse, O
影响因子：
5.5
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
通讯作者：
Rainger, G. Ed
影响因子：
2.8
作者：
GORDON, S;KESHAV, S;STEIN, M
通讯作者：
STEIN, M
DOI：
10.1084/jem.20132413
发表时间：
2014-06-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Finsterbusch M;Voisin MB;Beyrau M;Williams TJ;Nourshargh S
通讯作者：
Nourshargh S
影响因子：
15.9
作者：
DeLeo, FR;Renee, J;Nauseef, WM
通讯作者：
Nauseef, WM