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Differential migratory properties of monocytes isolated from human subjects naïve and non-naïve to Cannabis

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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.

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Abbreviations

CB:

Cannabinoid

eCB:

Endocannabinoid

pCB:

Phytocannabinoid

AEA:

Arachidonoylethanolamine

PEA:

Palmioylethanolamine

THC:

Tetrahydrocannabinol

CBN:

Cannabinol

CBD:

Cannabidiol

PBMC:

Peripheral blood mononuclear cell

CCL2:

C–C motif ligand 2 or monocyte chemo-attractant protein 1

References

  • Atwood BK, Mackie K (2010) CB2: a cannabinoid receptor with an identity crisis. Br J Pharmacol 160:467–479

    Article  PubMed  CAS  Google Scholar 

  • Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Huffman JW, Layward L (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404:84–87

    Article  PubMed  CAS  Google Scholar 

  • Castillo A, Tolon MR, Fernandez-Ruiz J, Romero J, Martinez-Orgado J (2010) The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol Dis 37:434–440

    Article  PubMed  CAS  Google Scholar 

  • Chong MS, Wolff K, Wise K, Tanton C, Winstock A, Silber E (2006) Cannabis use in patients with multiple sclerosis. Mult Scler 12:646–651

    Article  PubMed  CAS  Google Scholar 

  • Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4:399–418

    Article  PubMed  Google Scholar 

  • Conductier G, Blondeau N, Guyon A, Nahon JL, Rovere C (2010) The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 224:93–100

    Article  PubMed  CAS  Google Scholar 

  • Dawson J, Miltz W, Mir AK, Wiessner C (2003) Targeting monocyte chemoattractant protein-1 signalling in disease. Expert Opin Ther Targets 7:35–48

    Article  PubMed  CAS  Google Scholar 

  • Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res 29:313–326

    Article  PubMed  CAS  Google Scholar 

  • Doorenbos NJ (1971) Cultivation, extraction and analysis of Cannabis sativa L. Ann NY Acad Sci 191:3–14

    Google Scholar 

  • Fetterman PS, Keith ES, Waller CW, Guerrero O, Doorenbos NJ, Quimby MW (1971) Mississippi-grown Cannabis sativa L: preliminary observation on chemical definition of phenotype and variations in tetrahydrocannabinol content versus age, sex, and plant part. J Pharm Sci 60:1246–1249

    Article  PubMed  CAS  Google Scholar 

  • Franklin A, Stella N (2003) Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors. Eur J Pharmacol 474:195–198

    Article  PubMed  CAS  Google Scholar 

  • Fujita M, Kohanbash G, Fellows-Mayle W, Hamilton RL, Komohara Y, Decker SA, Ohlfest JR, Okada H (2011) COX-2 blockade suppresses gliomagenesis by inhibiting myeloid-derived suppressor cells. Cancer Res 71:2664–2674

    Article  PubMed  CAS  Google Scholar 

  • Garden GA, Moller T (2006) Microglia biology in health and disease. J Neuroimmune Pharmacol 1:127–137

    Article  PubMed  Google Scholar 

  • Geissmann F, Jung S, Littman DR (2003) Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19:71–82

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Navarro H, Vinue A, Vila-Caballer M, Fortuno A, Beloqui O, Zalba G, Burks D, Diez J, Andres V (2008) Molecular mechanisms of atherosclerosis in metabolic syndrome: role of reduced IRS2-dependent signaling. Arterioscler Thromb Vasc Biol 28:2187–2194

    Article  PubMed  CAS  Google Scholar 

  • Huang NL, Juang JM, Wang YH, Hsueh CH, Liang YJ, Lin JL, Tsai CT, Lai LP (2010) Rimonabant inhibits TNF-alpha-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway. Acta Pharmacol Sin 31:1447–1453

    Article  PubMed  CAS  Google Scholar 

  • Izzo AA, Borrelli F, Capasso R, Dimarzo V, Mechoulam R (2009) Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 30:515–527

    Article  PubMed  CAS  Google Scholar 

  • Kishimoto S, Gokoh M, Oka S, Muramatsu M, Kajiwara T, Waku K, Sugiura T (2003) 2-Arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism. J Biol Chem 278:24469–24475

    Article  PubMed  CAS  Google Scholar 

  • Klein TW, Cabral GA (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J Neuroimmune Pharmacol 1:50–64

    Article  PubMed  Google Scholar 

  • Kulkarni O, Anders HJ (2008) CCL2/MCP1: a novel target in systemic lupus erythematosus and lupus nephritis. Z Rheumatol 67:220–224

    Article  PubMed  CAS  Google Scholar 

  • Landucci E, Scartabelli T, Gerace E, Moroni F, Pellegrini-Giampietro DE (2011) CB1 receptors and post-ischemic brain damage: studies on the toxic and neuroprotective effects of cannabinoids in rat organotypic hippocampal slices. Neuropharmacology 60:674–682

    Article  PubMed  CAS  Google Scholar 

  • Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 105:2699–2704

    Article  PubMed  CAS  Google Scholar 

  • Mach F, Steffens S (2008) The role of the endocannabinoid system in atherosclerosis. J Neuroendocrinol 20(Suppl 1):53–57

    Article  PubMed  CAS  Google Scholar 

  • Mahad DJ, Ransohoff RM (2003) The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Semin Immunol 15:23–32

    Article  PubMed  CAS  Google Scholar 

  • Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, Ledent C, Cheng X, Carrier EJ, Mann MK, Giovannoni G, Pertwee RG, Yamamura T, Buckley NE, Hillard CJ, Lutz B, Baker D, Dittel BN (2007) Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 13:492–497

    Article  PubMed  CAS  Google Scholar 

  • Miller AM, Stella N (2008) CB2 receptor-mediated migration of immune cells: it can go either way. Br J Pharmacol 153:299–308

    Article  PubMed  CAS  Google Scholar 

  • Miller AM, Stella N (2009) Microglial cell migration stimulated by ATP and C5a involve distinct molecular mechanisms: quantification of migration by a novel near-infrared method. Glia 57:875–883

    Article  PubMed  Google Scholar 

  • Montecucco F, Burger F, Mach F, Steffens S (2008) CB2 cannabinoid receptor agonist JWH-015 modulates human monocyte migration through defined intracellular signaling pathways. Am J Physiol Heart Circ Physiol 294:H1145–H1155

    Article  PubMed  CAS  Google Scholar 

  • Ni X, Geller EB, Eppihimer MJ, Eisenstein TK, Adler MW, Tuma RF (2004) Win 55212–2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model. Mult Scler 10:158–164

    Article  PubMed  CAS  Google Scholar 

  • Nong L, Newton C, Cheng Q, Friedman H, Roth MD, Klein TW (2002) Altered cannabinoid receptor mRNA expression in peripheral blood mononuclear cells from marijuana smokers. J Neuroimmunol 127:169–176

    Article  PubMed  CAS  Google Scholar 

  • Patinkin D, Milman G, Breuer A, Fride E, Mechoulam R (2008) Endocannabinoids as positive or negative factors in hematopoietic cell migration and differentiation. Eur J Pharmacol 595:1–6

    Article  PubMed  CAS  Google Scholar 

  • Pertwee RG, Howlett AC, Abood ME, Alexander SP, Dimarzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol Rev 62:588–631

    Article  PubMed  CAS  Google Scholar 

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  PubMed  CAS  Google Scholar 

  • Prinz M, Priller J (2010) Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J Neuroimmunol 224:80–84

    Article  PubMed  CAS  Google Scholar 

  • Raborn ES, Cabral GA (2010) Cannabinoid inhibition of macrophage migration to the trans-activating (Tat) protein of HIV-1 is linked to the CB(2) cannabinoid receptor. J Pharmacol Exp Ther 333:319–327

    Article  PubMed  CAS  Google Scholar 

  • Raborn ES, Marciano-Cabral F, Buckley NE, Martin BR, Cabral GA (2008) The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor. J Neuroimmune Pharmacol 3:117–129

    Article  PubMed  Google Scholar 

  • Rossi S, Bernardi G, Centonze D (2010) The endocannabinoid system in the inflammatory and neurodegenerative processes of multiple sclerosis and of amyotrophic lateral sclerosis. Exp Neurol 224:92–102

    Article  PubMed  CAS  Google Scholar 

  • Roth MD, Baldwin GC, Tashkin DP (2002) Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem Phys Lipids 121:229–239

    Article  PubMed  CAS  Google Scholar 

  • Sacerdote P, Massi P, Panerai AE, Parolaro D (2000) In vivo and in vitro treatment with the synthetic cannabinoid CP55, 940 decreases the in vitro migration of macrophages in the rat: involvement of both CB1 and CB2 receptors. J Neuroimmunol 109:155–163

    Article  PubMed  CAS  Google Scholar 

  • Stella N (2010) Cannabinoid and cannabinoid-like receptors in microglia, astrocytes, and astrocytomas. Glia 58:1017–1030

    Article  PubMed  Google Scholar 

  • van de Veerdonk FL, Netea MG (2010) Diversity: a hallmark of monocyte society. Immunity 33:289–291

    Article  PubMed  Google Scholar 

  • Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405

    PubMed  CAS  Google Scholar 

  • Weiss JM, Downie SA, Lyman WD, Berman JW (1998) Astrocyte-derived monocyte-chemoattractant protein-1 directs the transmigration of leukocytes across a model of the human blood-brain barrier. J Immunol 161:6896–6903

    PubMed  CAS  Google Scholar 

  • Zhang M, Martin BR, Adler MW, Razdan RJ, Kong W, Ganea D, Tuma RF (2009) Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. J Neuroimmune Pharmacol 4:249–259

    Article  PubMed  Google Scholar 

  • Zhang H, Hilton DA, Hanemann CO, Zajicek J (2011) Cannabinoid receptor and N-acyl phosphatidylethanolamine phospholipase D-evidence for altered expression in multiple sclerosis. Brain Pathol 21(5):544–557

    PubMed  CAS  Google Scholar 

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Acknowledgments

Eric Horne and Jonathan Coy for assistance with microscopy. Funding to NS (DA014486) and to MS (F32AT005046, NCCAM).

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The authors declare that they have no competing interests.

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Correspondence to Michelle Sexton.

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Sexton, M., Silvestroni, A., Möller, T. et al. Differential migratory properties of monocytes isolated from human subjects naïve and non-naïve to Cannabis . Inflammopharmacol 21, 253–259 (2013). https://doi.org/10.1007/s10787-012-0133-9

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  • DOI: https://doi.org/10.1007/s10787-012-0133-9

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