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Role of cannabinoid receptors in inhibiting macrophage costimulatory activity.
Int Immunopharmacol. 2004 Feb; 4(2):265-78.II

Abstract

Delta(9)-tetrahydrocannabinol (THC) inhibits several immunologic functions of macrophages. THC's impact on peritoneal macrophages to deliver costimulatory signals to a helper T cell hybridoma was investigated by T cell interleukin-2 production stimulated with immobilized anti-CD3 antibody. The drug's inhibition of costimulatory activity depended on the macrophages. THC decreased costimulation provided by peritoneal cells elicited with polystyrene beads and thioglycollate, but the drug had no influence with macrophages elicited with thioglycollate alone. Bead administration induced CB2 mRNA expression in macrophages, while CB1 mRNA was not detected. Although inhibition was associated with functional heat-stable antigen, a costimulatory molecule, on macrophages, THC exposure did not alter cell surface heat-stable antigen expression. Inhibition by THC and anti-heat-stable antigen antibody was not additive suggesting the inhibitory mechanisms may overlap. Cannabinoid suppression was stereoselective; low affinity synthetic isomer CP56,667 did not diminish the T cell response. CB1-selective antagonist SR141716A completely reversed, and CB2-selective antagonist SR144528 partially blocked THC's inhibition. Both antagonists appeared to behave as inverse agonists in a receptor-selective manner. Although T cells expressed a low level of CB2 mRNA, neither THC nor SR141716A affected T cell activation in a system independent of macrophages, while SR144528 was inhibitory. High affinity synthetic agonist CP55,940, but not partial agonist THC, impaired costimulation by macrophages from mice lacking CB2 receptor. Although CB1 mRNA was not detected in CB2 null macrophages, CP55,940 reversed the inverse agonist activity of SR141716A. Hence, CB2 and possibly another receptor subtype may be involved in mediating cannabinoid suppression of macrophage costimulation.

Authors+Show Affiliations

Department of Microbiology and Immunology, MCV Station, Box 980678, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14996418

Citation

Chuchawankul, Siriporn, et al. "Role of Cannabinoid Receptors in Inhibiting Macrophage Costimulatory Activity." International Immunopharmacology, vol. 4, no. 2, 2004, pp. 265-78.
Chuchawankul S, Shima M, Buckley NE, et al. Role of cannabinoid receptors in inhibiting macrophage costimulatory activity. Int Immunopharmacol. 2004;4(2):265-78.
Chuchawankul, S., Shima, M., Buckley, N. E., Hartmann, C. B., & McCoy, K. L. (2004). Role of cannabinoid receptors in inhibiting macrophage costimulatory activity. International Immunopharmacology, 4(2), 265-78.
Chuchawankul S, et al. Role of Cannabinoid Receptors in Inhibiting Macrophage Costimulatory Activity. Int Immunopharmacol. 2004;4(2):265-78. PubMed PMID: 14996418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of cannabinoid receptors in inhibiting macrophage costimulatory activity. AU - Chuchawankul,Siriporn, AU - Shima,Mika, AU - Buckley,Nancy E, AU - Hartmann,Constance B, AU - McCoy,Kathleen L, PY - 2003/04/03/received PY - 2003/04/23/revised PY - 2003/12/16/accepted PY - 2004/3/5/pubmed PY - 2004/12/16/medline PY - 2004/3/5/entrez SP - 265 EP - 78 JF - International immunopharmacology JO - Int Immunopharmacol VL - 4 IS - 2 N2 - Delta(9)-tetrahydrocannabinol (THC) inhibits several immunologic functions of macrophages. THC's impact on peritoneal macrophages to deliver costimulatory signals to a helper T cell hybridoma was investigated by T cell interleukin-2 production stimulated with immobilized anti-CD3 antibody. The drug's inhibition of costimulatory activity depended on the macrophages. THC decreased costimulation provided by peritoneal cells elicited with polystyrene beads and thioglycollate, but the drug had no influence with macrophages elicited with thioglycollate alone. Bead administration induced CB2 mRNA expression in macrophages, while CB1 mRNA was not detected. Although inhibition was associated with functional heat-stable antigen, a costimulatory molecule, on macrophages, THC exposure did not alter cell surface heat-stable antigen expression. Inhibition by THC and anti-heat-stable antigen antibody was not additive suggesting the inhibitory mechanisms may overlap. Cannabinoid suppression was stereoselective; low affinity synthetic isomer CP56,667 did not diminish the T cell response. CB1-selective antagonist SR141716A completely reversed, and CB2-selective antagonist SR144528 partially blocked THC's inhibition. Both antagonists appeared to behave as inverse agonists in a receptor-selective manner. Although T cells expressed a low level of CB2 mRNA, neither THC nor SR141716A affected T cell activation in a system independent of macrophages, while SR144528 was inhibitory. High affinity synthetic agonist CP55,940, but not partial agonist THC, impaired costimulation by macrophages from mice lacking CB2 receptor. Although CB1 mRNA was not detected in CB2 null macrophages, CP55,940 reversed the inverse agonist activity of SR141716A. Hence, CB2 and possibly another receptor subtype may be involved in mediating cannabinoid suppression of macrophage costimulation. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/14996418/Role_of_cannabinoid_receptors_in_inhibiting_macrophage_costimulatory_activity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(03)00298-4 DB - PRIME DP - Unbound Medicine ER -