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The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5: Linkage to the CB2 Receptor

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Abstract

The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB2 receptor-specific antagonist SR144528 but not by the CB1 receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB2 knockout mice. Collectively, these results suggest that cannabinoids act through the CB2 receptor to transdeactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB2 receptor may be a constituent element of a network of G protein-coupled receptor signal transductional systems, inclusive of chemokine receptors, that act coordinately to modulate macrophage migration.

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Acknowledgement

The authors thank Ms. Christina L. Hartman for excellent technical assistance. These studies were supported through NIH Awards DA015608, DA05832, DA05274 and T32 DA07027.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, 1101 E. Marshall St., Richmond, VA, 23298-0678, USA

    Erinn S. Raborn, Francine Marciano-Cabral & Guy A. Cabral

  2. Biological Sciences Department, California State Polytechnic University, Pomona, CA, 91768, USA

    Nancy E. Buckley

  3. Departments of Pharmacology and Toxicology, Virginia Commonwealth University, School of Medicine, Richmond, VA, 23298, USA

    Francine Marciano-Cabral, Billy R. Martin & Guy A. Cabral

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  1. Erinn S. Raborn
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Correspondence to Guy A. Cabral.

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Raborn, E.S., Marciano-Cabral, F., Buckley, N.E. et al. The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5: Linkage to the CB2 Receptor. J Neuroimmune Pharmacol 3, 117–129 (2008). https://doi.org/10.1007/s11481-007-9077-z

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