Characterization of endocannabinoid-mediated induction of myeloid-derived suppressor cells involving mast cells and MCP-1

Austin R. Jackson, Venkatesh L. Hegde, Prakash S. Nagarkatti, Mitzi Nagarkatti

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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 KitW/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.

Original languageEnglish (US)
Pages (from-to)609-619
Number of pages11
JournalJournal of Leukocyte Biology
Volume95
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • Anandamide
  • CB1
  • Chemokine
  • Monocytic MDSCs

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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