A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences.
A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences.
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DOI：
10.1080/10739680902942271
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Sarelius IH
中科院分区：
文献类型：
--
作者：
Sumagin R;Lamkin-Kennard KA;Sarelius IH
粘附分子表达的变化在调节白细胞行为中起着关键作用，但流体剪切对这些相互作用的贡献不容忽视。在这里，我们剖析了每个因素对不同小静脉区域白细胞行为的影响。使用活体共聚焦显微镜对麻醉小鼠提睾肌的血液灌注微血管网络中的白细胞行为进行定量。使用 ICAM-1 荧光标记、荧光颗粒跟踪和计算流体动力学对 ICAM-1 表达和流体剪切率进行量化。 TNFα 诱导 ICAM-1 表达增加，并消除了不同大小对照小静脉之间观察到的差异。因此，所有血管尺寸的白细胞粘附均增加至相似水平（5.1±0.46 个白细胞/100μm 对比 2.1±0.47 个[对照]），但在小静脉会聚处仍显着较高（7.8±0.4）。白细胞迁移主要发生在最小的小静脉和小静脉会聚处（分别为23.9±5.1和31.9±2.7个白细胞/10,000μm2组织）。在小静脉会聚中，预计两个入口血管会形成一个低速区域，从而增加白细胞粘附的可能性。在不同大小微静脉的直线区域中，ICAM-1 表达的变异性解释了白细胞行为的差异；在会聚区域，流体剪切可能对白细胞-EC 相互作用产生更大的影响。
Variation in expression of adhesion molecules plays a key role in regulating leukocyte behavior, but the contribution of fluid shear to these interactions cannot be ignored. Here we dissected the effects of each of these factors on leukocyte behavior in different venular regions. Leukocyte behavior was quantified in blood perfused microvascular networks in anesthetized mouse cremaster muscle using intravital confocal microscopy. ICAM-1 expression and fluid shear rate were quantified using ICAM-1 fluorescent labeling, fluorescent particle tracking, and computational fluid dynamics. TNFα-induced an increase in ICAM-1 expression, and abolished the differences observed among control venules of different sizes. Consequently, leukocyte adhesion was increased to a similar level across all vessel sizes (5.1±0.46 leukocytes/100μm vs. 2.1±0.47 [control]), but remained significantly higher in venular convergences (7.8±0.4). Leukocyte transmigration occurred primarily in the smallest venules and venular convergences (23.9±5.1 and 31.9±2.7 leukocytes/10,000μm2 tissue, respectively). In venular convergences the two inlet vessels are predicted to create a region of low velocity, increasing leukocyte adhesion probability. In straight regions of different sized venules the variability in ICAM-1 expression accounts for the differences in leukocyte behavior; in converging regions, fluid shear potentially has a greater effect on leukocyte-EC interactions.
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