Role of the atypical chemoattractant receptor CRAM in regulating CCL19 induced CCR7 responses in B-cell chronic lymphocytic leukemia

Molecular Cancer

Research

Julie Catusse¹  Katja Zirlik¹  Marion Leick¹  Maike V Buchner¹  Meike Burger¹  Mareike Groch¹  David J Clark² 

[1] Department of Hematology and Oncology, University Clinic of Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany;Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, University of London, Keppel St, WC1E 7HT, London, UK;

关键词: Chronic Lymphocytic Leukemia;    Chemokine Receptor;    Primary Central Nervous System Lymphoma;    Chronic Lymphocytic Leukemia Patient;    Secondary Lymphoid Organ;   

DOI  :  10.1186/1476-4598-9-297

 received in 2010-04-15, accepted in 2010-11-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsIn 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.ConclusionsWe 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.

【 授权许可】

Unknown   
© Catusse et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.