A beneficial aspect of a CB1 cannabinoid receptor antagonist: SR141716A isa potent inhibitor of macrophage infection by the intracellular pathogen Brucella suis

The psychoactive component of marijuana, Delta(9)-tetrahydrocannabinol (THC ) suppresses different functions of immunocytes, including the antimicrobic idal activity of macrophages. The triggering of cannabinoid receptors of CB 1 and CB2 subtypes present on leukocytes may account for these effects. We investigated the influence of specific CB1 or CB2 receptor antagonists (SR1 41716A and SR144528, respectively) and nonselective CB1/CB2 cannabinoid rec eptor agonists (CP55,940 or WIN 55212-2) on macrophage infection by Brucell a suis, an intracellular gramnegative bacteria. None of the compounds teste d affected bacterial phagocytosis. By contrast, the intracellular multiplic ation of Brucella was dose-dependently inhibited in cells treated with 10-5 00 nM SR141716A and 1 mu M SR141716A-induced cells exerted a potent microbi cidal effect against the bacteria. SR144528, CP55,940, or WIN 55212-2 did n ot affect (or slightly potentiated) the growth of phagocytized bacteria. Ho wever, CP55,940 or WIN 55212-2 reversed the SR141716A-mediated effect, whic h strongly suggested an involvement of macrophage CB1 receptors in the phen omenon. SR141716A was able to pre-activate macrophages and to trigger an ac tivation signal that inhibited Brucella development. The participation of e ndogenous cannabinoid ligand(s) in Brucella. infection was discussed. Final ly, our data show that SR141716A up-regulates the antimicrobial properties of macrophages in vitro and might be a pharmaceutical compound useful for c ounteracting the development of intramacrophagic gram-negative bacteria.