delta-9-Tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of Bacillus Calmétte-Guérin-activated macrophages.
The effect of delta-9-tetrahydrocannabinol (delta-9-THC), the major psychoactive component of marijuana, on the capacity of Bacillus Calmétte-Guérin (BCG)-activated macrophages to lyse L929 tumor cells, Naegleria fowleri amoebae, and herpes simplex virus-infected cells was examined. Delta-9-THC inhibited tumoricidal and amoebicidal activity in a dose-related manner. Antiviral activity was decreased when mice received 25 and 50 mg/kg delta-9-THC. The cannabinoid did not directly suppress the activation of macrophages as determined by levels of 5'-nucleotidase activity and did not inhibit splenic T-lymphocytes of BCG-recipient mice from producing interferon gamma. Nomarski optics microscopy, scanning electron microscopy, and radiolabeling binding studies demonstrated that macrophages from delta-9-THC-treated mice retained their capacity to attach to their targets. These results suggest that delta-9-THC suppresses cell contact-dependent amoebicidal, tumoricidal, and antiviral activities of activated macrophages at a stage following effector cell-target cell conjugation.
Medical College of Virginia/Virginia Commonwealth University, Department of Microbiology and Immunology, Richmond 23298.
D
D
Burnette-Curley
F
F
Marciano-Cabral
K
K
Fischer-Stenger
G A
GA
Cabral
D015720:5'-Nucleotidase / Q000032:analysis; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice
D001500:BCG Vaccine; D013759:Dronabinol; D007371:Interferon-gamma; D015720:5'-Nucleotidase