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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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The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5: Linkage to the CB2 Receptor
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Journal Article
The Cannabinoid Delta-9-tetrahydrocannabinol Mediates Inhibition of Macrophage Chemotaxis to RANTES/CCL5: Linkage to the CB2 Receptor
2008
Overview
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 CB
2
receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB
1
receptor-selective ligand ACEA had a minimal effect. The THC-mediated inhibition was reversed by the CB
2
receptor-specific antagonist SR144528 but not by the CB
1
receptor-specific antagonist SR141716A. In addition, THC treatment had a minimal effect on the chemotactic response of peritoneal macrophages from CB
2
knockout mice. Collectively, these results suggest that cannabinoids act through the CB
2
receptor to transdeactivate migratory responsiveness to RANTES/CCL5. Furthermore, the results suggest that the CB
2
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.
Publisher
Springer US
Subject
/ Arachidonic Acids - pharmacology
/ Biomedical and Life Sciences
/ Chemokine CCL5 - antagonists & inhibitors
/ Cyclohexanols - pharmacology
/ Female
/ Macrophages, Peritoneal - drug effects
/ Macrophages, Peritoneal - physiology
/ Mice
/ Receptor, Cannabinoid, CB1 - biosynthesis
/ Receptor, Cannabinoid, CB1 - drug effects
/ Receptor, Cannabinoid, CB1 - physiology
/ Receptor, Cannabinoid, CB2 - biosynthesis
/ Receptor, Cannabinoid, CB2 - deficiency
/ Receptor, Cannabinoid, CB2 - drug effects
/ Receptor, Cannabinoid, CB2 - physiology
/ Receptors, CCR1 - biosynthesis
/ Receptors, CCR5 - biosynthesis
/ Receptors, G-Protein-Coupled - physiology
/ RNA, Messenger - biosynthesis
/ Signal Transduction - physiology
/ Virology
