1 research outputs found
Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol
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