title: Differential migratory properties of monocytes isolated from human subjects naïve and non-naïve to Cannabis.
abstract: This study evaluates the migratory potential of monocytes isolated from two groups of human subjects: naïve and non-naïve to Cannabis. Phytocannabinoids (pCB), the bioactive agents produced by the plant Cannabis, regulate the phenotype and function of immune cells by interacting with CB1 and CB2 receptors. It has been shown that agents influencing the phenotype of circulating monocytes influence the phenotype of macrophages and the outcome of immune responses. To date, nothing is known about the acute and long-term effects of pCB on human circulating monocytes. Healthy subjects were recruited for a single blood draw. Monocytes were isolated, fluorescently labeled and their migration quantified using a validated assay that employs near infrared fluorescence and modified Boyden chambers. CB1 and CB2 receptor mRNA expression was quantified by qPCR. Monocytes from all subjects (n = 10) responded to chemokine (c-c motif) ligand 2 (CCL2) and human serum stimuli. Acute application of pCB significantly inhibited both the basal and CCL2-stimulated migration of monocytes, but only in subjects non-naïve to Cannabis. qPCR analysis indicates that monocytes from subjects non-naïve to Cannabis express significantly more CB1 mRNA. The phenotype of monocytes isolated from subjects non-naïve to Cannabis is significantly different from monocytes isolated from subjects naïve to Cannabis. Only monocytes from subjects non-naïve to Cannabis respond to acute exposure to pCB by reducing their overall migratory capacity. Our study suggests that chronic exposure to Cannabis affects the phenotype of circulating monocytes and accordingly could influence outcome of inflammatory responses occurring in injured tissues.
authors.affiliation: Department of Pharmacology, University of Washington, 1959 NE Pacific St., BB-1538, HSC, Box 357280, Seattle, WA 98195, USA. msexton@bastyr.edu
authors.forename: Michelle
authors.initials: M
authors.lastname: Sexton
authors.forename: Aurelio
authors.initials: A
authors.lastname: Silvestroni
authors.forename: Thomas
authors.initials: T
authors.lastname: Möller
authors.forename: Nephi
authors.initials: N
authors.lastname: Stella
mesh_terms: D000328:Adult; D002186:Cannabinoids / Q000008:administration & dosage / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry*; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D055815:Young Adult
chemical_list: D002186:Cannabinoids; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2