Splice variants of tissue factor promote monocyte-endothelial interactions by triggering the expression of cell adhesion molecules via integrin-mediated signaling.
Splice variants of tissue factor promote monocyte-endothelial interactions by triggering the expression of cell adhesion molecules via integrin-mediated signaling.
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DOI：
10.1111/j.1538-7836.2011.04454.x
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Bogdanov VY
中科院分区：
文献类型：
--
作者：
Srinivasan R;Ozhegov E;van den Berg YW;Aronow BJ;Franco RS;Palascak MB;Fallon JT;Ruf W;Versteeg HH;Bogdanov VY
TF在癌性和动脉粥样硬化病变中高度表达。单核细胞募集是这些病理状态下疾病进展的标志。研究整合素信号在内皮细胞TF依赖性募集单核细胞中的作用。检测flTF和asTF在宫颈癌和动脉粥样硬化病变中的表达。评估了原代微血管内皮细胞（MVEC）暴露于截短的flTF胞外域（LZ-TF）和重组asTF的生物学效应。flTF和asTF在癌病变和富脂斑块中表现出几乎相同的表达模式。肿瘤病变以及基质CD 68+单核细胞/巨噬细胞表达两种TF形式。原代MVEC与asTF和LZ-TF的粘附速度较快，且可被抗β1整合素抗体完全阻断。asTF-和LZ-TF-治疗MVEC促进粘附外周血单核细胞（PBMC）在眼眶剪切条件下，层流下，asTF引起的粘附比LZ-TF引起的更明显。表达谱分析和蛋白质印迹法显示，在MVEC中的细胞粘附分子（CAM）的广泛激活asTF治疗后，包括E-选择素，ICAM-1，和VCAM-1。在transwell试验中，在MCP-1梯度下，asTF增强PMBC通过MVEC单层的迁移约3倍。TF剪接变异体连接MVEC上的β1整合素，其诱导MVEC中CAM的表达并导致单核细胞粘附和跨内皮迁移。asTF在引起这些作用方面似乎比flTF更有效。我们的研究结果强调了非蛋白水解，整合素介导的信号传导的两个自然发生的TF变异体在癌症和动脉粥样硬化的病理生理意义。
TF is highly expressed in cancerous and atherosclerotic lesions. Monocyte recruitment is a hallmark of disease progression in these pathological states. To examine the role of integrin signaling in TF-dependent recruitment of monocytes by endothelial cells. The expression of flTF and asTF in cervical cancer and atherosclerotic lesions was examined. Biologic effects of the exposure of primary microvascular endothelial cells (MVEC) to truncated flTF ectodomain (LZ-TF) and recombinant asTF were assessed. flTF and asTF exhibited nearly identical expression patterns in cancer lesions and lipid-rich plaques. Tumor lesions as well as stromal CD68+ monocytes/macrophages expressed both TF forms. Primary MVEC rapidly adhered to asTF and LZ-TF, and this was completely blocked by anti-β1 integrin antibody. asTF- and LZ-TF-treatment of MVEC promoted adhesion of peripheral blood mononuclear cells (PBMC) under orbital shear conditions and under laminar flow; asTF-elicited adhesion was more pronounced than that elicited by LZ-TF. Expression profiling and western blotting revealed a broad activation of cell adhesion molecules (CAMs) in MVEC following asTF treatment including E-selectin, ICAM-1, and VCAM-1. In transwell assays, asTF potentiated PMBC migration through MVEC monolayers by ~3 fold under MCP-1 gradient. TF splice variants ligate β1 integrins on MVEC, which induces the expression of CAMs in MVEC and leads to monocyte adhesion and transendothelial migration. asTF appears more potent than flTF in eliciting these effects. Our findings underscore the pathophysiologic significance of non-proteolytic, integrin-mediated signaling by the two naturally occurring TF variants in cancer and atherosclerosis.
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影响因子：
5.5
作者：
Chandradas, Sajiv;Deikus, Gintaras;Bogdanov, Vladimir Y.
通讯作者：
Bogdanov, Vladimir Y.
影响因子：
7.5
作者：
Grosser, Marianne;Magdolen, Viktor;Albrecht, Sybille
通讯作者：
Albrecht, Sybille
影响因子：
7.5
作者：
Sovershaev, M. A.;Egorina, E. M.;Hansen, J. B.
通讯作者：
Hansen, J. B.
影响因子：
5.3
作者：
Wilson HM
通讯作者：
Wilson HM
影响因子：
37.8
作者：
Borissoff, Julian Ilcheff;Heeneman, Sylvia;Spronk, Henri M. H.
通讯作者：
Spronk, Henri M. H.