Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo.

Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo.
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DOI:
10.1084/jem.194.2.205
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发表时间:
2001-07-16
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Lindbom L
Lindbom L
中科院分区:
其他
文献类型:
--
作者:
Eriksson EE;Xie X;Werr J;Thoren P;Lindbom L

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在白细胞外渗的多步骤过程中,白细胞与内皮细胞建立初始接触的机制尚不清楚。同时,关于L-选择素在白细胞募集中的作用也存在争议。在这里,使用活体显微镜,我们研究了白细胞从自由流动直接到内皮的捕获(初级捕获),以及通过在小静脉、细胞因子刺激的动脉血管和动脉粥样硬化病变中与滚动的白细胞的相互作用而介导的捕获(二级捕获)。与小静脉相比,动脉血管中的捕获物更为突出。在小静脉中,随着血管直径和管壁剪切率的增加,捕获的发生率增加。二次捕获需要最小的滚动白细胞流量,在所有研究的血管类型中,∼对总捕获的贡献为20-50%。在动脉中,二次捕获诱导形成成簇和串的滚动的白细胞。L-选择素的功能抑制阻断了二次捕获,从而降低了动脉血管和大静脉(直径45μm)中滚动白细胞的流量,但不能减少小静脉(45μm)中滚动白细胞的流量。这些发现证明了从体内的自由流动中捕获白细胞的重要性。不同直径范围、滚动流量和切变率的小静脉对次级捕获的阻断作用不同,解释了关于L-选择素在不同的白细胞募集情况下的作用的争议。更重要的是,动脉粥样硬化病变发生二次捕获,这一事实为L-选择素在动脉粥样硬化形成过程中白细胞聚集中的作用提供了第一个证据。
In the multistep process of leukocyte extravasation, the mechanisms by which leukocytes establish the initial contact with the endothelium are unclear. In parallel, there is a controversy regarding the role for L-selectin in leukocyte recruitment. Here, using intravital microscopy in the mouse, we investigated leukocyte capture from the free flow directly to the endothelium (primary capture), and capture mediated through interactions with rolling leukocytes (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on atherosclerotic lesions in the aorta. Capture was more prominent in arterial vessels compared with venules. In venules, the incidence of capture increased with increasing vessel diameter and wall shear rate. Secondary capture required a minimum rolling leukocyte flux and contributed by ∼20–50% of total capture in all studied vessel types. In arteries, secondary capture induced formation of clusters and strings of rolling leukocytes. Function inhibition of L-selectin blocked secondary capture and thereby decreased the flux of rolling leukocytes in arterial vessels and in large (>45 μm in diameter), but not small (<45 μm), venules. These findings demonstrate the importance of leukocyte capture from the free flow in vivo. The different impact of blockage of secondary capture in venules of distinct diameter range, rolling flux, and wall shear rate provides explanations for the controversy regarding the role of L-selectin in various situations of leukocyte recruitment. What is more, secondary capture occurs on atherosclerotic lesions, a fact that provides the first evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.
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