Heterogeneity in the Locomotory Behavior of Human Monocyte Subsets over Human Vascular Endothelium In Vitro
Heterogeneity in the Locomotory Behavior of Human Monocyte Subsets over Human Vascular Endothelium In Vitro
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DOI：
10.4049/jimmunol.1401806
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发表时间：
2015-08-01
影响因子：
4.4
通讯作者：
Peakman, Mark
中科院分区：
文献类型：
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作者：
Collison, Joanna L.;Carlin, Leo M.;Peakman, Mark
人单核细胞包括三个不同的亚群，由其CD 14和CD 16的相对表达定义。这些亚群似乎在体内平衡和炎症中具有不同的功能作用，但对它们与大血管和微血管内皮细胞相互作用的方式知之甚少，这是实现其功能作用的关键组成部分。在本研究中，我们研究了三个主要的人类单核细胞亚群在人内皮细胞单层的运动行为进行生理相关水平的剪切流在体外。每个子集被证明在休息状态下优先执行不同类型的运动行为。在CD 14（+）CD 16（-）和CD 14（dim）CD 16（+）单核细胞中观察到与鼠Ly 6C（-）单核细胞的“巡逻”行为相似的长距离爬行行为，但在CD 14（+）CD 16（+）单核细胞中未观察到。CD 14（dim）CD 16（+）和CD 14（+）CD 16（-）单核细胞表现出对微血管内皮的粘附优于大血管内皮，而CD 14（+）CD 16（+）单核细胞表现出相反的粘附。在30分钟观察期内，在CD 14（dim）CD 16（+）单核细胞中未观察到跨内皮迁移。CD 14（dim）CD 16（+）单核细胞的长距离爬行行为通过阻断ICAM 1、VCAM 1或CX（3）CL 1而被消除，而CD 14（+）CD 16（-）单核细胞的这种行为只需要ICAM 1。这些研究表明存在亚型特异性的人单核细胞迁移行为模式，具有明显的粘附分子依赖性，这可能有助于阐明其生理功能和与疾病的相关性。
Human monocytes comprise three distinct subsets, defined by their relative expression of CD14 and CD16. These subsets appear to have different functional roles within homeostasis and inflammation, but little is known about the manner in which they interact with macro- and microvascular endothelial cells, a key enabling component for the fulfillment of their functional roles. In the present study, we examined the locomotory behavior of the three major human monocyte subsets over human endothelial monolayers subjected to physiologically relevant levels of shear flow in vitro. Each subset was shown to preferentially perform different types of locomotory behavior in a resting state. A long-range crawling behavior, similar to the "patrolling" behavior of murine Ly6C(-) monocytes, was observed in CD14(+)CD16(-) and CD14(dim) CD16(+) monocytes, but not in CD14(+)CD16(+) monocytes. CD14(dim)CD16(+) and CD14(+)CD16(-) monocytes showed a preference for adhering to microvascular over macrovascular endothelium, whereas CD14(+)CD16(+) monocytes showed the opposite. Transendothelial migration was not observed in CD14(dim)CD16(+) monocytes during the 30-min observation period. Long-range crawling behavior in CD14(dim)CD16(+) monocytes was abrogated by blockade of ICAM1, VCAM1, or CX(3)CL1, in contrast with CD14(+)CD16(-) monocytes, which only required ICAM1 for this behavior. These studies indicate the existence of subtype-specific human monocyte migratory behavior patterns with distinct adhesion molecule dependence, which may assist in elucidating their physiological function and relevance to disease.