Role of the atypical chemoattractant receptor CRAM in regulating CCL19 induced CCR7 responses in B-cell chronic lymphocytic leukemia.
Role of the atypical chemoattractant receptor CRAM in regulating CCL19 induced CCR7 responses in B-cell chronic lymphocytic leukemia.
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DOI：
10.1186/1476-4598-9-297
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发表时间：
2010-11-22
期刊：
影响因子：
37.3
通讯作者：
Burger M
中科院分区：
文献类型：
--
作者：
Catusse J;Leick M;Groch M;Clark DJ;Buchner MV;Zirlik K;Burger M
非信号趋化因子受体，包括受体DARC、D6和CCX-CKR，最近被证明参与趋化因子的清除和活性调节。人类趋化因子受体CRAM（也称为HCR或CCRL2）是最近发现的这一非典型群体的成员。CRAM在B细胞上以成熟阶段依赖的方式表达，而在T细胞上不表达。我们最近发现它可以竞争性地结合CCL19。CCL19及其信号受体CCR7是参与细胞向次级淋巴器官募集和成熟的关键成分。B细胞慢性淋巴细胞白血病（B- cll）是一种以增生性中心（或假滤泡）为特征的低度淋巴瘤。增生中心的发展是由于异常的细胞定位，它们参与恶性细胞的发展。CCR7在CLL患者的B细胞上高表达，并介导向其配体CCL19和CCL21的迁移，而CRAM的表达及其对CCR7的潜在干扰尚不清楚。在这项研究中，我们发现来自B- cll患者的B细胞表现出高度可变的CRAM表达程度，而CCR7的表达水平则更为一致。我们研究了一种假设，即与非典型受体DARC类似，CRAM可以调节趋化因子的可用性和/或功效，从而调节细胞活化。我们发现高水平的CRAM表达不利于CCL19的有效趋化。CCL19诱导的map -激酶磷酸化和细胞内钙释放也被CRAM表达改变。此外，我们证明了CCL19信号的调控是随时间维持的。我们假设CRAM是一个参与CCR7/CCL19介导反应微调/控制的因子。这种调节对于CCL19诱导增殖中心的形成，支持T/B细胞相遇以及B- cll疾病进展的关键作用至关重要。
The non-signalling chemokine receptors, including receptors DARC, D6 and CCX-CKR, have recently been shown to be involved in chemokine clearance and activity regulation. The human chemokine receptor CRAM (also known as HCR or CCRL2) is the most recently identified member of this atypical group. CRAM is expressed on B cells in a maturation-stage dependent manner and absent on T cells. We have recently shown that it competitively binds CCL19. CCL19 and its signalling receptor CCR7 are critical components involved in cell recruitment to secondary lymphoid organs and in maturation. B cell Chronic Lymphocytic Leukemia (B-CLL) is a low-grade lymphoma characterized by proliferative centres (or pseudofollicles). Proliferative centres develop due to abnormal cellular localisation and they are involved in the development of malignant cells. CCR7 is highly expressed on B cells from CLL patients and mediates migration towards its ligands CCL19 and CCL21, while CRAM expression and potential interferences with CCR7 are yet to be characterized. In this study, we show that B cells from patients with B-CLL present highly variable degrees of CRAM expression in contrast to more consistently high levels of CCR7. We investigated the hypothesis that, similar to the atypical receptor DARC, CRAM can modulate chemokine availability and/or efficacy, resulting in the regulation of cellular activation. We found that a high level of CRAM expression was detrimental to efficient chemotaxis with CCL19. MAP-kinase phosphorylation and intracellular calcium release induced by CCL19 were also altered by CRAM expression. In addition, we demonstrate that CRAM-induced regulation of CCL19 signalling is maintained over time. We postulate that CRAM is a factor involved in the fine tuning/control of CCR7/CCL19 mediated responses. This regulation could be critical to the pivotal role of CCL19 induced formation of proliferation centres supporting the T/B cells encounter as well as disease progression in B-CLL.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
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作者：
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DOI：
10.1124/jpet.302.1.290
发表时间：
2002-07-01
影响因子：
3.5
作者：
Christopherson, KW;Campbell, JJ;Hromas, RA
通讯作者：
Hromas, RA