title: The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor.
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.
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University, School of Medicine, 1101 E. Marshall St., Richmond, VA 23298-0678, USA.
authors.forename: Erinn S
authors.initials: ES
authors.lastname: Raborn
authors.forename: Francine
authors.initials: F
authors.lastname: Marciano-Cabral
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Buckley
authors.forename: Billy R
authors.initials: BR
authors.lastname: Martin
authors.forename: Guy A
authors.initials: GA
authors.lastname: Cabral
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors*; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D003511:Cyclohexanols / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis / Q000172:deficiency / Q000187:drug effects* / Q000502:physiology; D054389:Receptors, CCR1 / Q000096:biosynthesis / Q000235:genetics; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D000077285:Rimonabant; D015398:Signal Transduction / Q000502:physiology
chemical_list: C531961:1-(4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl)-3-methylcyclohexanol; D001095:Arachidonic Acids; D001892:Camphanes; C515301:Ccr1 protein, mouse; D018946:Chemokine CCL5; D003511:Cyclohexanols; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D043562:Receptors, G-Protein-Coupled; C110630:SR 144528; C119325:arachidonyl-2-chloroethylamide; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant