Collison Joanna L, Carlin Leo M, Eichmann Martin, Geissmann Frederic, Peakman Mark
Peter Gorer Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London, London SE1 9RT, United Kingdom; and.
Centre for Molecular and Cellular Biology of Inflammation, Faculty of Life Sciences & Medicine, King's College London, London SE1 9RT, United Kingdom.
J Immunol. 2015 Aug 1;195(3):1162-70. doi: 10.4049/jimmunol.1401806. Epub 2015 Jun 17.
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 CX3CL1, 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.
人类单核细胞包含三个不同的亚群，由它们CD14和CD16的相对表达来定义。这些亚群在体内稳态和炎症过程中似乎具有不同的功能作用，但对于它们与大、微血管内皮细胞相互作用的方式却知之甚少，而内皮细胞是它们发挥功能作用的关键支持成分。在本研究中，我们检测了三种主要人类单核细胞亚群在体外承受生理相关水平剪切流的人内皮细胞单层上的运动行为。结果显示，每个亚群在静息状态下优先表现出不同类型的运动行为。在CD14(+)CD16(-)和CD14(dim)CD16(+)单核细胞中观察到一种远距离爬行行为，类似于小鼠Ly6C(-)单核细胞的“巡逻”行为，但在CD14(+)CD16(+)单核细胞中未观察到。CD14(dim)CD16(+)和CD14(+)CD16(+)单核细胞表现出优先粘附于微血管内皮而非大血管内皮的倾向，而CD14(+)CD16(-)单核细胞则表现出相反的倾向。在30分钟的观察期内，未在CD14(dim)CD16(+)单核细胞中观察到跨内皮迁移。与仅需要ICAM1来进行这种行为的CD14(+)CD16(-)单核细胞相比，阻断ICAM1、VCAM1或CX3CL1可消除CD14(dim)CD16(+)单核细胞中的远距离爬行行为。这些研究表明存在具有不同粘附分子依赖性的亚型特异性人类单核细胞迁移行为模式，这可能有助于阐明它们的生理功能以及与疾病的相关性。
