Cannabinoid Inhibition of the Processing of Intact Lysozyme by Macrophages: Evidence for CB2 Receptor Participation

• Published in: The Journal of pharmacology and experimental therapeutics 1999-06, Vol.289 (3), p.1620-1625
• Main Authors: McCoy, K L, Matveyeva, M, Carlisle, S J, Cabral, G A
• Format: Article
• Language: English
• Subjects: Animals; Cannabinoids - pharmacology; Cyclohexanols - pharmacology; Dronabinol - pharmacology; Hybridomas; Interleukin-2 - biosynthesis; Lymphocyte Activation - drug effects; Macrophages - drug effects; Macrophages - enzymology; Macrophages - physiology; Mice; Muramidase - metabolism; Receptors, Cannabinoid; Receptors, Drug - genetics; Receptors, Drug - physiology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - physiology; T-Lymphocytes, Helper-Inducer - drug effects; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - physiology; Transcription, Genetic - drug effects
• ISSN: 0022-3565; 1521-0103

Delta 9 -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.