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首页> 外文期刊>American Journal of Physiology >Functional and genomic changes induced by alveolar transmigration in human neutrophils.
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Functional and genomic changes induced by alveolar transmigration in human neutrophils.

机译：肺泡移行在人类嗜中性粒细胞中诱导的功能和基因组变化。

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Although the accumulation of neutrophils in the lungs and airways is common to many inflammatory lung diseases, including acute lung injury, the alterations that neutrophils undergo as they leave the peripheral circulation and migrate into the lungs have not been well characterized. Human volunteers were exposed to endotoxin by bronchoscopic instillation. The resulting air space neutrophil accumulation and peripheral blood neutrophils were isolated 16 h later, compared with circulating neutrophils isolated before or after to the pulmonary endotoxin exposure, and compared with circulating neutrophils exposed to endotoxin in vitro. Microarray analysis was performed on air space, circulatory, and in vitro endotoxin-stimulated neutrophils. Functional analysis included the determination of neutrophil apoptosis, chemotaxis, release of cytokines and growth factors, and superoxide anion release. Dramatic gene expression differences were apparent between air space and circulating neutrophils: approximately 15% of expressed genes have altered expression levels, including broad increases in inflammatory- and chemotaxis-related genes, as well as antiapoptotic and IKK-activating pathways. Functional analysis of air space compared with circulating neutrophils showed increased superoxide release, diminished apoptosis, decreased IL-8-induced chemotaxis, and a pattern of IL-8, macrophage inflammatory protein-1beta, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha release different from either unstimulated or LPS-stimulated circulating neutrophils. Many of these changes are not elicited by in vitro treatment with endotoxin. Limited differences were detected between circulating neutrophils isolated before and 16 h after pulmonary endotoxin instillation. These results suggest that neutrophils sequestered in the lung become fundamentally different from those resident in the circulation, and this difference is distinct from in vitro activation with endotoxin.
机译：尽管嗜中性粒细胞在肺和气道中的积累是许多炎症性肺病（包括急性肺损伤）所共有的，但嗜中性粒细胞离开外周循环并迁移到肺中时所经历的改变尚未得到很好的表征。人类志愿者通过支气管镜滴注暴露于内毒素。与在暴露于肺内毒素之前或之后分离出的循环中性粒细胞相比，在16小时后分离出了空域中性粒细胞积累和外周血中性粒细胞，并与体外暴露于内毒素的循环中性粒细胞进行了比较。在空气空间，循环系统和体外内毒素刺激的中性粒细胞上进行微阵列分析。功能分析包括中性粒细胞凋亡，趋化性，细胞因子和生长因子释放以及超氧阴离子释放的测定。气隙和循环中性粒细胞之间存在明显的基因表达差异：大约15％的表达基因改变了表达水平，包括炎症和趋化性相关基因的广泛增加，以及抗凋亡和IKK激活途径。与循环中性粒细胞相比，对空域的功能分析显示超氧化物释放增加，凋亡减少，IL-8诱导的趋化性降低以及IL-8，巨噬细胞炎性蛋白1β，单核细胞趋化蛋白1和肿瘤坏死因子- α释放不同于未刺激或LPS刺激的循环中性粒细胞。这些变化中的许多变化不是通过用内毒素进行体外治疗引起的。在肺内毒素滴注之前和之后16 h分离的循环中性粒细胞之间检测到有限的差异。这些结果表明，隔离在肺中的嗜中性粒细胞与驻留在循环中的嗜中性粒细胞从根本上是不同的，并且这种差异不同于体外用内毒素激活。

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