Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoyglycerol
| Autor: | Ruud Delwel, Sandra E. Verbakel, M. Maccarrone, Meritxell Alberich Jordà, Peter J. M. Valk, Allessandro Finazzi-Agrò, Yolanda Vankan-Berkhoudt, Bob Löwenberg |
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| Přispěvatelé: | Hematology |
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Cannabinoid receptor Myeloid Receptors Drug Immunology Arachidonic Acids Thymus Gland Biology Ligands Transfection Biochemistry Glycerides Mice Internal medicine Cannabinoid Receptor Modulators medicine Cannabinoid receptor type 2 Tumor Cells Cultured Animals Drug Interactions Myeloid Cells Receptor Receptors Cannabinoid B-Lymphocytes Cannabinoids Chemotaxis Myeloid leukemia Cell Biology Hematology medicine.disease Molecular biology Leukemia Haematopoiesis medicine.anatomical_structure Endocrinology Leukemia Myeloid Cytokines lipids (amino acids peptides and proteins) Spleen Endocannabinoids |
| Zdroj: | Blood, 99, 2786-2793. American Society of Hematology |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.V99.8.2786 |
| Popis: | Cb2 is a novel protooncogene encoding the peripheral cannabinoid receptor. Previous studies demonstrated that 2 distinct noncoding first exons exist: exon-1A and exon-1B, which both splice to protein-coding exon-2. We demonstrate that in retrovirally induced murine myeloid leukemia cells with proviral insertion in Cb2, exon-1B/exon-2 Cb2 messenger RNA levels have been increased, resulting in high receptor numbers. In myeloid leukemia cells without virus insertion in this locus, low levels of only exon-1A/exon-2 Cb2 transcripts were present and receptors could not be detected. To elucidate the function of Cb2 in myeloid leukemia cells, a set of in vitro experiments was carried out using 32D/G-CSF-R (granulocyte colony-stimulating factor receptor) cells transfected with exon-1B/exon-2 Cb2 complementary DNA and a myeloid cell line carrying a virus insertion in Cb2 (ie, NFS 78). We demonstrate that a major function of the Cb2 receptor is stimulation of migration as determined in a transwell assay. Exposure of Cb2-expressing cells to different cannabinoids showed that the true ligand for Cb2 is 2-arachidonoylglycerol (2-AG), which may act as chemoattractant and as a chemokinetic agent. Furthermore, we observed a significant synergistic activity between 2-AG and interleukin-3 or G-CSF, suggesting cross-talk between the different receptor systems. Radioactive-ligand binding studies revealed significant numbers of Cb2 receptors in normal spleen. Transwell experiments carried out with normal mouse spleen cells showed 2-AG-induced migration of B220-, CD19-, immunoglobulin M-, and immunoglobulin D-expressing B lymphocytes. Our study demonstrates that a major function of Cb2 receptor expressed on myeloid leukemia cells or normal splenocytes is stimulation of migration. |
| Databáze: | OpenAIRE |
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