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Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation.
J Pharmacol Exp Ther. 1999 Jun; 289(3):1620-5.JP

Abstract

Delta9-tetrahydrocannabinol (THC) impairs multiple immunological functions. The ability of a macrophage hybridoma to function as an antigen-presenting cell was examined by the stimulation of a soluble protein antigen-specific helper T cell hybridoma to secrete interleukin-2. THC exposure significantly reduced the T cell response to the native form of the antigen after a 24-h pretreatment of the macrophages with nanomolar drug concentrations. However, THC did not affect interleukin-2 production when the macrophages presented a synthetic peptide of the antigen to the T cells, suggesting that the drug may interfere with antigen processing, not peptide presentation. Cannabinoid inhibition of the T cell response to the native antigen was stereoselective consistent with the involvement of a cannabinoid (CB) receptor. Bioactive CP-55,940 diminished T cell activation, whereas the inactive stereoisomer CP-56,667 did not. The macrophage hybridoma expressed mRNA for the CB2 but not the CB1 receptor whereas the T cells expressed an extremely low level of mRNA for the CB2 receptor. The CB1-selective antagonist SR141716A did not reverse the suppression caused by THC, demonstrating that the CB1 receptor was not responsible for the drug's inhibitory effect. In contrast, the CB2-selective antagonist SR144528 completely blocked THC's suppression of the T cell response, implicating the participation of the CB2 receptor. These findings suggest that the CB2 receptor may be involved in CB inhibition of antigen processing by macrophages in this system.

Authors+Show Affiliations

Department of Microbiology and Immunology, Medical College of Virginia of Virginia Commonwealth University, Richmond, Virginia, USA. kmccoy@hsc.vcu.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

10336560

Citation

McCoy, K L., et al. "Cannabinoid Inhibition of the Processing of Intact Lysozyme By Macrophages: Evidence for CB2 Receptor Participation." The Journal of Pharmacology and Experimental Therapeutics, vol. 289, no. 3, 1999, pp. 1620-5.
McCoy KL, Matveyeva M, Carlisle SJ, et al. Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. J Pharmacol Exp Ther. 1999;289(3):1620-5.
McCoy, K. L., Matveyeva, M., Carlisle, S. J., & Cabral, G. A. (1999). Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. The Journal of Pharmacology and Experimental Therapeutics, 289(3), 1620-5.
McCoy KL, et al. Cannabinoid Inhibition of the Processing of Intact Lysozyme By Macrophages: Evidence for CB2 Receptor Participation. J Pharmacol Exp Ther. 1999;289(3):1620-5. PubMed PMID: 10336560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation. AU - McCoy,K L, AU - Matveyeva,M, AU - Carlisle,S J, AU - Cabral,G A, PY - 1999/5/21/pubmed PY - 1999/5/21/medline PY - 1999/5/21/entrez SP - 1620 EP - 5 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 289 IS - 3 N2 - Delta9-tetrahydrocannabinol (THC) impairs multiple immunological functions. The ability of a macrophage hybridoma to function as an antigen-presenting cell was examined by the stimulation of a soluble protein antigen-specific helper T cell hybridoma to secrete interleukin-2. THC exposure significantly reduced the T cell response to the native form of the antigen after a 24-h pretreatment of the macrophages with nanomolar drug concentrations. However, THC did not affect interleukin-2 production when the macrophages presented a synthetic peptide of the antigen to the T cells, suggesting that the drug may interfere with antigen processing, not peptide presentation. Cannabinoid inhibition of the T cell response to the native antigen was stereoselective consistent with the involvement of a cannabinoid (CB) receptor. Bioactive CP-55,940 diminished T cell activation, whereas the inactive stereoisomer CP-56,667 did not. The macrophage hybridoma expressed mRNA for the CB2 but not the CB1 receptor whereas the T cells expressed an extremely low level of mRNA for the CB2 receptor. The CB1-selective antagonist SR141716A did not reverse the suppression caused by THC, demonstrating that the CB1 receptor was not responsible for the drug's inhibitory effect. In contrast, the CB2-selective antagonist SR144528 completely blocked THC's suppression of the T cell response, implicating the participation of the CB2 receptor. These findings suggest that the CB2 receptor may be involved in CB inhibition of antigen processing by macrophages in this system. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10336560/Cannabinoid_inhibition_of_the_processing_of_intact_lysozyme_by_macrophages:_evidence_for_CB2_receptor_participation_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10336560 DB - PRIME DP - Unbound Medicine ER -