Cannabinoid inhibition of the processing of intact lysozyme by macrophages: evidence for CB2 receptor participation.
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.
McCoy
K L
KL
Department of Microbiology and Immunology, Medical College of Virginia of Virginia Commonwealth University, Richmond, Virginia, USA. kmccoy@hsc.vcu.edu
Matveyeva
M
M
Carlisle
S J
SJ
Cabral
G A
GA
D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D006825:Hybridomas; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D051379:Mice; D009113:Muramidase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D002186:Cannabinoids; D003511:Cyclohexanols; D007376:Interleukin-2; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D009113:Muramidase