α(M)β(2)-integrin-intercellular adhesion molecule-1 interactions drive the flow-dependent trafficking of Guillain-Barré syndrome patient derived mononuclear leukocytes at the blood-nerve barrier in vitro.
α(M)β(2)-integrin-intercellular adhesion molecule-1 interactions drive the flow-dependent trafficking of Guillain-Barré syndrome patient derived mononuclear leukocytes at the blood-nerve barrier in vitro.
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DOI：
10.1002/jcp.24100
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发表时间：
2012-12
影响因子：
5.6
通讯作者：
Ubogu, Eroboghene E.
中科院分区：
文献类型：
--
作者：
Yosef, Nejla;Ubogu, Eroboghene E.
血原性白细胞在人血-神经屏障（BNB）上运输的机制在很大程度上是未知的。细胞间粘附分子-1（ICAM-1）参与了格林-巴利综合征（GBS）的发病机制。我们使用原代神经内膜内皮细胞开发了一种马槟榔碱激活的体外人BNB模型。用10 U/mL组织坏死因子-α和20 U/mL干扰素-γ进行内皮处理导致促炎趋化因子CCL 2、CXCL 9、CXCL 11和CCL 20的从头表达，CXCL 2 -3、CXCL 8和CXCL 10的表达相对于基础水平增加。细胞因子治疗诱导/增强ICAM-1，E-和P-选择素，血管细胞粘附分子-1和选择性剪接的前粘附纤连蛋白变体，纤连蛋白连接片段-1表达的时间依赖性的方式，没有改变连接粘附分子-A的表达。来自未经治疗的GBS患者的淋巴细胞和单核细胞表达ICAM-1反配体αM-和α L-整联蛋白，与健康对照相比，α M-整联蛋白表达具有差异调节。在模拟体内毛细血管血液动力学的流动条件下，相对于未处理状态，细胞因子处理后BNB处的总GBS患者和健康对照单核白细胞粘附/迁移增加>3倍。抗人α M-整合素（CD 11b）和ICAM-1的功能中和单克隆抗体使未经治疗的GBS患者单核白细胞在BNB的运输分别减少59%和64.2%。抗α L-整合素（CD 11 a）单克隆抗体和人静脉注射免疫球蛋白分别使总白细胞粘附/迁移减少22.8%和17.6%。本研究证明了α M-整合素对GBS循环单核细胞的差异调节，以及α M-整合素-ICAM-1相互作用在体外人BNB的致病性GBS患者白细胞运输中的重要作用。
The mechanisms of hematogenous leukocyte trafficking at the human blood-nerve barrier (BNB) are largely unknown. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the pathogenesis of Guillain-Barré syndrome (GBS). We developed a cytokine-activated human in vitro BNB model using primary endoneurial endothelial cells. Endothelial treatment with 10 U/mL tissue necrosis factor-α and 20 U/mL interferon-γ resulted in de novo expression of proinflammatory chemokines CCL2, CXCL9, CXCL11 and CCL20, with increased expression of CXCL2-3, CXCL8 and CXCL10 relative to basal levels. Cytokine treatment induced/ enhanced ICAM-1, E- and P-selectin, vascular cell adhesion molecule-1 and the alternatively spliced pro-adhesive fibronectin variant, fibronectin connecting segment-1 expression in a time-dependent manner, without alterations in junctional adhesion molecule-A expression. Lymphocytes and monocytes from untreated GBS patients express ICAM-1 counterligands, αM- and αL-integrin, with differential regulation of αM-integrin expression compared to healthy controls. Under flow conditions that mimic capillary hemodynamics in vivo, there was a >3-fold increase in total GBS patient and healthy control mononuclear leukocyte adhesion/ migration at the BNB following cytokine treatment relative to the untreated state. Function neutralizing monoclonal antibodies against human αM-integrin (CD11b) and ICAM-1 reduced untreated GBS patient mononuclear leukocyte trafficking at the BNB by 59% and 64.2% respectively. Monoclonal antibodies against αL-integrin (CD11a) and human intravenous immunoglobulin reduced total leukocyte adhesion/migration by 22.8% and 17.6% respectively. This study demonstrates differential regulation of αM-integrin on circulating mononuclear cells in GBS, as well as an important role for αM-integrin-ICAM-1 interactions in pathogenic GBS patient leukocyte trafficking at the human BNB in vitro.
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影响因子：
14.5
作者：
Kieseier, BC;Tani, M;Hartung, HP
通讯作者：
Hartung, HP
影响因子：
14.5
作者：
BELL, MA;WEDDELL, AGM
通讯作者：
WEDDELL, AGM
影响因子：
14.5
作者：
Enders, U;Lobb, R;Gold, R
通讯作者：
Gold, R
影响因子：
6
作者：
Hartung, Hans-Peter
通讯作者：
Hartung, Hans-Peter
影响因子：
9.9
作者：
Hadden, RDM;Karch, H;Toyka, KV
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Toyka, KV