Recruitment mechanisms of primary and malignant B cells to the human liver
Recruitment mechanisms of primary and malignant B cells to the human liver
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DOI：
10.1002/hep.25790
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发表时间：
2012-10-01
期刊：
影响因子：
13.5
通讯作者：
Adams, David H.
中科院分区：
文献类型：
--
作者：
Shetty, Shishir;Bruns, Tony;Adams, David H.
B细胞存在于慢性炎症的肝组织中，最近的证据表明它们与肝病的进展有关。此外，很大比例的肝脏淋巴瘤是B细胞起源的。调节正常和恶性B细胞从血液重新聚集到外周组织的分子信号知之甚少，这导致我们在基于血流的黏附分析中研究人类B细胞通过肝窦内皮细胞的迁移。在这种检测中，人的血液来源的B细胞从剪切流中被捕获，而不是之前的滚动阶段，并由血管细胞黏附分子-1(VCAM-1)介导的牢固的黏附。与在内皮上表现出旺盛爬行行为的T细胞不同，B细胞在一定比例的细胞间黏附分子-1(ICAM-1)、血管黏附蛋白-1、普通淋巴管内皮和血管内皮受体-1/稳定素-1以及趋化因子受体CXCR3和CXCR4的组合介导下，保持静止状态。来自慢性淋巴细胞白血病和边缘带B细胞淋巴瘤患者的B细胞淋巴瘤细胞株和原代恶性B细胞也表现出ICAM-1和/或VCAM-1参与的整合素介导的牢固黏附，并表现出ICAM-1依赖的形状改变和爬行行为。与原代淋巴细胞不同，恶性细胞不进行跨内皮细胞迁移，这可以解释为什么淋巴瘤经常以恶性细胞在肝窦内的血管内聚集为特征。结论：我们的研究结果表明，不同的信号组合促进了B细胞向肝脏的募集，这表明可能有新的靶点来调节疾病中的肝脏炎症。淋巴细胞归巢的某些特征在淋巴瘤向肝脏的重新聚集中保持，这表明淋巴细胞重新聚集的治疗靶点也可能防止肝脏淋巴瘤的扩散。(2012国际肝病)
B cells are present within chronically inflamed liver tissue and recent evidence implicates them in the progression of liver disease. In addition, a large proportion of hepatic lymphomas are of B-cell origin. The molecular signals that regulate normal and malignant B-cell recruitment into peripheral tissue from blood are poorly understood, leading us to study human B-cell migration through hepatic sinusoidal endothelial cells in flow-based adhesion assays. In such assays, human blood-derived B cells were captured from shear flow without a previous rolling phase and underwent firm adhesion mediated by vascular cell adhesion molecule-1 (VCAM-1). Unlike T cells, which displayed vigorous crawling behavior on the endothelium, B cells remained static before a proportion underwent transendothelial migration mediated by a combination of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion protein-1, common lymphatic endothelial and vascular endothelial receptor-1/stabilin-1, and the chemokine receptors, CXCR3 and CXCR4. B-cell lymphoma cell lines and primary malignant B cells from patients with chronic lymphocytic leukemia and marginal zone B cell lymphoma also underwent integrin-mediated firm adhesion involving ICAM-1 and/or VCAM-1 and demonstrated ICAM-1-dependent shape-change and crawling behavior. Unlike primary lymphocytes, the malignant cells did not undergo transendothelial migration, which could explain why lymphomas are frequently characterized by the intravascular accumulation of malignant cells in the hepatic sinusoids. Conclusion: Our findings demonstrate that distinct combinations of signals promote B-cell recruitment to the liver, suggesting the possibility of novel targets to modulate liver inflammation in disease. Certain features of lymphocyte homing are maintained in lymphoma recruitment to the liver, suggesting that therapeutic targets for lymphocyte recruitment may also prevent hepatic lymphoma dissemination. (HEPATOLOGY 2012)