Journal of Neuroimmune Pharmacology

, Volume 6, Issue 4, pp 540–545

Chronic Δ-9-tetrahydrocannabinol Administration Increases Lymphocyte CXCR4 Expression in Rhesus Macaques

  • Nicole J. LeCapitaine
  • Ping Zhang
  • Peter Winsauer
  • Edith Walker
  • Curtis Vande Stouwe
  • Constance Porretta
  • Patricia E. Molina
BRIEF REPORT

Abstract

Cannabinoids have been reported to produce various immunomodulatory effects, which could potentially impact the host response to bacterial or viral infection. We have recently demonstrated that chronic Δ-9-tetrahydrocannabinol (THC; 0.32 mg/kg i.m., BID) decreased early mortality in rhesus macaques infected with simian immunodeficiency virus (SIV). However, the possibility that prolonged THC administration affects lymphocyte counts, phenotype, and proliferation indices has not been addressed. We examined expression of proliferative and phenotypic markers in circulating lymphocytes of male young adult rhesus macaques chronically-treated with THC (i.m. twice daily 0.32 mg/kg) for 12 months. Chronic THC administration did not alter lymphocyte subtypes, naïve and memory subsets, proliferation, or apoptosis of T lymphocytes when compared to time-matched vehicle-treated controls. However, chronic THC increased T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes compared to control. These results show that chronic THC administration produces changes in T cell phenotype, which can potentially contribute to host immunomodulation to infectious challenges.

Keywords

Flow cytometry Lymphocytes Cannabinoids CXCR4 Rhesus macaques 

References

  1. Bleul CC, Wu L, Hoxie JA, Springer TA, Mackay CR (1997) The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci 94(5):1925–1930PubMedCrossRefGoogle Scholar
  2. Borner C, Smida M, Hollt V, Schraven B, Kraus J (2009) Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T cell receptor-triggered signaling. J Biol Chem 284:35450–35460PubMedCrossRefGoogle Scholar
  3. Condie R, Herring A, Koh WS, Lee M, Kaminski NE (1996) Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2. J Biol Chem 271(22):13175–13183PubMedCrossRefGoogle Scholar
  4. Cristillo AD, Highbarger HC, Dewar RL, Dimitrov DS, Golding H, Bierer BE (2002) Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element. FASEB J 16:354–364PubMedCrossRefGoogle Scholar
  5. Dion ML, Poulin JF, Bordi R, Sylvestre M, Corsini R, Kettaf N, Dalloul A, Boulassel MR, Debre P, Routy JP, Grossman Z, Sekaly RP, Cheynier R (2004) HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation. Immunity 21:757–768PubMedCrossRefGoogle Scholar
  6. Jia W, Hegde VL, Singh NP, Sisco D, Grant S, Nagarkatti M, Nagarkatti PS (2006) D9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol Cancer Res 4(8):549–562PubMedCrossRefGoogle Scholar
  7. Kawakami Y, Klein TW, Newton C, Djeu JY, Dennert G, Specter S, Friedman H (1988) Suppression by cannabinoids of a cloned cell line with natural killer cell activity. Proc Soc Exp Biol Med 187(3):355–359PubMedGoogle Scholar
  8. Klein TW, Newton C, Larsen K, Lu L, Perkins I, Nong L, Friedman H (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74(4):486–496PubMedCrossRefGoogle Scholar
  9. Kurihara R, Tohyama Y, Matsusaka S, Naruse H, Kinoshita E, Tsujioka T, Katsumata Y, Yamamura H (2006) Effects of peripheral cannabinoid receptor ligands on motility and polarization in neutrophil-like HL60 cells and human neutrophils. J Biol Chem 281(18):12908–12918PubMedCrossRefGoogle Scholar
  10. Molina PE, Winsauer P, Zhang P, Walker E, Birke L, Amedee AM, Vande Stouwe C, Troxclair D, McGoey R, Varner K, Byerley L, Lamotte L (2010) Cannabinoid administration attenuates the progression of simian immunodeficiency virus. AIDS Res Hum Retrovir. doi:10.1089/aid.2010.0218 PubMedGoogle Scholar
  11. Murikinati S, Juttler E, Keinert T, Ridder DA, Muhammad S, Waibler Z, Ledent C, Zimmer A, Kalinke U, Schwaninger M (2010) Activation of cannabinoid 2 receptors protects against cerebral ischemia by inhibiting neutrophil recruitment. FASEB J 24(3):788–798PubMedCrossRefGoogle Scholar
  12. Nahas GG, Moirishima A, Desoize B (1977) Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Fed Proc 36:1748–1752PubMedGoogle Scholar
  13. Petersen BH, Graham J, Lemberger L (1976) Marijuana, tetrahydrocannabinol and T-cell function. Life Sci 19:395–400PubMedCrossRefGoogle Scholar
  14. Phillips R, Ager A (2002) Activation of pertussis toxin-sensitive CXCL12 (SDF-1) receptors mediates transendothelial migration of T lymphocytes across lymph node high endothelial cells. Eur J Immunol 32(3):837–847PubMedCrossRefGoogle Scholar
  15. Pross S, Klein T, Newton C, Smith J, Widen R, Friedman H (1990) Differential suppression of T-cell subpopulations by THC (delta-9-tetrahydrocannabinol). Int J Immunopharmacol 12:539–544.PubMedCrossRefGoogle Scholar
  16. Rock RB, Gekker G, Hu S, Sheng WS, Cabral GA, Martin BR (2007) WIN55,212-2-mediated inhibition of HIV-1 expression in microglial cells: involvement of cannabinoid receptors. J Neuroimmune Pharmacol 2:178–183PubMedCrossRefGoogle Scholar
  17. Sopper S, Nierwetberg D, Halbach A, Sauer U, Scheller C, Stahl-Hennig C, Matz-Rensing K, Schafer F, Schneider T, ter Meulen V, Muller JG (2003) Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys. Blood 101:1213–1219PubMedCrossRefGoogle Scholar
  18. Schuitemaker H, Koot M, Kootstra NA, Dercksen MW, deGoede RE, van Steenwijk RP, Lange JM, Schattenkerk JK, Miedema F, Tersmette M (1992) Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell tropic virus populations. J Virol 66:1354–1360PubMedGoogle Scholar
  19. Shay AH, Choi R, Whittaker K, Salehi K, Kitchen CM, Tashkin DP, Roth MD, Balwin CG (2003) Impairement of antimicrobial activity and nitric oxide production in alveolar macrophages from smokers of marijuana and cocaine. J Infect Dis 187(4):700–704PubMedCrossRefGoogle Scholar
  20. Tindall B, Cooper DA, Donovan B, Barnes T, Philpot CR, Gold J, Penny R (1988) The Sydney AIDS project: development of acquired immunodeficiency syndrome in a group of HIV seropositive homosexual men. Aust N Z J Med 18:8–15PubMedCrossRefGoogle Scholar
  21. Wallace JM, Oishi JS, Barbers RG, Simmons MS, Tashkin DP (1994) Lymphocytic subpopulation profiles in bronchoalveolar lavage fluid and peripheral blood from tobacco and marijuana smokers. Chest 105:847–852PubMedCrossRefGoogle Scholar
  22. Winsauer PJ, Molina PE, Amedee AM, Filipeanu CM, McGoey RR, Troxclair DA, Walker EM, Birke LL, Vande Stouwe C, Howard JM, Leonard ST, Moerschbaecher JM, and Lewis PB (2011) Tolerance to chronic delta-9-tetrahydrocannabinol (Δ9-THC) in Rhesus Macaques infected with simian immunodeficiency virus. Exp and Clin Psychopharm (in press)Google Scholar
  23. White SC, Brin SC, Janicki BW (1975) Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers. Science 188:71–72PubMedCrossRefGoogle Scholar
  24. Yuan M, Kiertscher S, Cheng Q, Zoumalan R, Tashkin D, Roth M (2002) Delta-9-tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J Neuroimmunol 133:124–131PubMedCrossRefGoogle Scholar
  25. Zhu W, Friedman H, Klein TW (1998) Δ9-Tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. J Pharmacol Exp Ther 286:1103–1109PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Nicole J. LeCapitaine
    • 1
    • 3
    • 4
  • Ping Zhang
    • 5
  • Peter Winsauer
    • 2
    • 3
    • 4
  • Edith Walker
    • 1
    • 3
    • 4
  • Curtis Vande Stouwe
    • 1
    • 3
    • 4
  • Constance Porretta
    • 3
    • 4
  • Patricia E. Molina
    • 1
    • 3
    • 4
  1. 1.Department of PhysiologyLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Department of PharmacologyLouisiana State University Health Sciences CenterNew OrleansUSA
  3. 3.Department of MedicineLouisiana State University Health Sciences CenterNew OrleansUSA
  4. 4.Alcohol and Drug Abuse Center of ExcellenceLouisiana State University Health Sciences CenterNew OrleansUSA
  5. 5.Department of SurgeryMichigan State UniversityEast LansingUSA

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