| First Author | Jackson AR | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 95 |
| Issue | 4 | Pages | 609-19 |
| PubMed ID | 24319288 | Mgi Jnum | J:211870 |
| Mgi Id | MGI:5576827 | Doi | 10.1189/jlb.0613350 |
| Citation | Jackson AR, et al. (2014) Characterization of endocannabinoid-mediated induction of myeloid-derived suppressor cells involving mast cells and MCP-1. J Leukoc Biol 95(4):609-19 |
| abstractText | Endocannabinoids are lipid-signaling molecules found in the nervous system; however, their precise role in the periphery is unclear. In the current study, we observed that a single i.p. administration of AEA caused rapid induction of MDSCs. The MDSCs contained a mixture of granulocytic and monocytic subtypes and expressed Arg-1 and iNOS. The MDSCs suppressed T cell proliferation in vitro and used iNOS to mediate their effect. Moreover, adoptive transfer of MDSCs led to suppression of mBSA-induced DTH. Through the use of pharmacological inhibition, as well as genetic knockout mice, we found that the induction of MDSCs by AEA was CB1-dependent. The induction of MDSCs by AEA was reduced significantly in mast cell-deficient mice, while maintained in LPS-insensitive mice, showing that the induction of MDSCs by AEA was dependent, at least in part, on mast cells and independent of TLR4. Chemokine analysis of AEA- treated WT mice showed an early spike of MCP-1, which was decreased in Kit(W/W-sh) mice, showing a role of mast cells in the secretion of MCP-1 in response to AEA. Also, use of antibodies against MCP-1 or mice deficient in MCP-1 confirmed the role played by MCP-1. Interestingly, MCP-1 played a significant role in the induction of monocytic but not granulocytic MDSCs. Our studies demonstrate for the first time that endocannaboinids activate CB1 on mast cells to induce MCP-1, which facilitates recruitment of monocytic MDSCs. |
