Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration
Identification of a phenotypically and functionally distinct population of long-lived neutrophils in a model of reverse endothelial migration
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DOI：
10.1189/jlb.0905496
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发表时间：
2006-02-01
影响因子：
5.5
通讯作者：
Rainger, G. Ed
中科院分区：
文献类型：
--
作者：
Buckley, Christopher D.;Ross, Ewan A.;Rainger, G. Ed
近期研究表明，中性粒细胞并非是一种同质的细胞群体。在此，我们鉴定出了人类中性粒细胞的一个亚群，其具有独特的细胞表面受体特征[高表达CD54，低表达CXC趋化因子受体1（CXCR1低表达）]，这些细胞是穿过内皮单层迁移后又通过反向迁移（RT）重新出现的细胞。当与内皮细胞接触时，反向迁移的中性粒细胞可避免凋亡，表现出功能性激活，并且在流变学特性上与未经历跨内皮迁移的中性粒细胞不同。在体内，全身性炎症患者外周血中1 - 2%的中性粒细胞呈现反向迁移表型。健康供体中也存在一小部分（约0.25%）。反向迁移的中性粒细胞不同于未接触过外界的循环中性粒细胞（CD54低表达，CXCR1高表达）以及经甲酰甲硫氨酰 - 亮氨酰 - 苯丙氨酸激活后的未接触过外界的细胞（CD54低表达，CXCR1低表达）。重要的是，反向迁移表型（CD54高表达，CXCR1低表达）也不同于组织驻留中性粒细胞（CD54低表达，CXCR1低表达）。我们的研究结果表明，中性粒细胞能够以逆行方向穿过内皮细胞迁移，并提示在人体内的外周循环中存在一群具有独特表型和功能且有组织接触经历的中性粒细胞。
Recent studies have demonstrated that neutrophils are not a homogenous population of cells. Here, we have identified a subset of human neutrophils with a distinct profile of cell-surface receptors [CD54(high), CXC chemokine receptor 1(low) (CXCR1(low))], which represent cells that have migrated through an endothelial monolayer and then re-emerged by reverse transmigration (RT). RT neutrophils, when in contact with endothelium, were rescued from apoptosis, demonstrate functional priming, and were rheologically distinct from neutrophils that had not undergone transendothelial migration. In vivo, 1-2% of peripheral blood neutrophils in patients with systemic inflammation exhibit a RT phenotype. A smaller population existed in healthy donors (approximate to 0.25%). RT neutrophils were distinct from naive circulatory neutrophils (CD54(low), CXCR1(high)) and naive cells after activation with formyl-Met-Leu-Phe (CD54(low), CXCR1(low)). It is important that the RT phenotype (CD54(high), CXCR1(low)) is also distinct from tissue resident neutrophils (CD54(low), CXCR1(low)). Our results demonstrate that neutrophils can migrate in a retrograde direction across endothelial cells and suggest that a population of tissue-experienced neutrophils with a distinct phenotype and function are present in the peripheral circulation in humans in vivo.