Delta-9-tetrahydrocannabinol-(THC)-mediated inhibition of macrophage macromolecular metabolism is antagonized by human serum proteins and by cell surface proteins.
Our previous study demonstrated THC-inhibited DNA synthesis and the phagocytic activity of P388D1 cells [Tang, Lancz, Specter & Bullock (1992) Int. J. Immunopharmac., 14, 253-262]. The ability of proteins in human and bovine sera and of constitutive cellular proteins to modulate the biologic activity of THC was investigated. Both human and fetal bovine sera antagonized a THC-mediated inhibition of P388D1 cell DNA synthesis in a dose-dependent manner. This antagonism was proportional to the protein concentration present in the medium. Both albumin and gamma-globulins influenced THC's inhibitory effects, although they were less potent alpha/beta serum lipoproteins. Exclusion of fatty acid moieties from the albumin did not diminish its ability to antagonize THC. Tritium-labeled THC was acid precipitable only after incubation with bovine or human serum albumin but not DNA, suggesting a physical interaction between the cannabinoid and the protein. Further studies showed that pre-treating cells with trypsin to remove surface proteins significantly enhanced the inhibitory activity of sub-toxic concentrations of THC. Thus, the data indicate that the magnitude of THC's biological effects is determined by the presence and concentration of soluble proteins in the microenvironment and by constitutive proteins present on the cell surface.
Tang
J L
JL
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Lancz
G
G
Specter
S
S
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D013759:Dronabinol / Q000037:antagonists & inhibitors*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice
D001798:Blood Proteins; D008565:Membrane Proteins; D013759:Dronabinol; D004247:DNA