Attenuation of CXCR4 responses by CCL18 in acute lymphocytic leukemia B cells
| Autor: | Percy Schröttner, Julie Catusse, Marion Leick, Meike Burger, S. Wollner, Ingrid U. Schraufstatter |
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| Rok vydání: | 2010 |
| Předmět: |
Receptors
CXCR4 Chemokine Physiology Clinical Biochemistry Apoptosis Biology Ligands Lymphocyte Activation Transfection Receptors G-Protein-Coupled Lymphocyte chemotaxis Cell Line Tumor Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Chlorocebus aethiops medicine Animals Humans Calcium Signaling Receptor B cell Cell Proliferation Estradiol Precursor Cells B-Lymphoid Estrogen Antagonists CCL18 Chemotaxis Cell Biology Chemokine CXCL12 Recombinant Proteins Chemotaxis Leukocyte Haematopoiesis medicine.anatomical_structure Receptors Estrogen Chemokines CC COS Cells Immunology Cancer research biology.protein Cell activation Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 225:792-800 |
| ISSN: | 0021-9541 |
| DOI: | 10.1002/jcp.22284 |
| Popis: | CCL18 and CXCL12 are homeostatic chemokines with high constitutive concentrations in serum. Elevated levels of CCL18 have been described in various diseases including childhood acute lymphocytic leukemia (ALL) but its functions remain poorly characterized. Its receptor has not been identified, but functional cellular responses like lymphocyte chemotaxis have been described. CXCL12 is a pivotal chemokine for hematopoiesis and B cell homing processes. We demonstrate that CCL18 interferes with CXCL12-mediated pre-B ALL cell activation. CXCL12-induced calcium mobilization, chemotaxis, pseudo-emperipolesis and cellular proliferation could be significantly reduced by CCL18 in pre-B ALL cell lines. The results could be observed in primary cells from patients suffering from pre-B ALL, but not in cells from patients suffering from common ALL. Direct effects of CCL18 on the receptor for CXCL12, CXCR4, could be excluded. Moreover, we found that CCL18 modulations of CXCL12-induced responses are mediated through the chemokine-like receptor GPR30. CCL18 bound to GPR30 expressing cells, and antibodies against GPR30 abolished this binding as well as CCL18-mediated functional effects. We also observed that, CCL18 interferes with the activation of GPR30 by previously identified ligands (17β-estradiol and chemical agonists). We therefore suggest that CCL18 is an important modulator of CXCR4-dependent responses in pre-B ALL cells via interactions with GPR30. |
| Databáze: | OpenAIRE |
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