Suppressive Effect of  9-Tetrahydrocannabinol in Vitro on Phagocytosis by Murine Macrophages

Friedman, Michelle; Cepero, Mayra Lopez; Klein, Thomas; Friedman, Herman

doi:10.3181/00379727-182-42332

Cited by 25 publications

(9 citation statements)

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“…Although, there have been reports indicating that the endocannabinoid system is important in regulating DC biology (Table 1), detailed studies addressing the effects of cannabinoids on cellular processes in DC are relatively scarce. In macrophages, however, it was shown that cannabinoids affect phagocytosis, NO- and cytokine production as well as the capacity to process and present soluble peptide antigens [52,53,54,55,56]. Although, not formely proven, it is possible that cannabinoids affect DC functions in similar ways to that reported for macrophages.…”

Section: Cannabinoids and Modulation Of Dendritic Cell Functionmentioning

confidence: 98%

Dendritic Cell Regulation by Cannabinoid-Based Drugs

2010

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Cannabinoid pharmacology has made important advances in recent years after the cannabinoid system was discovered. Studies in experimental models and in humans have produced promising results using cannabinoid-based drugs for the treatment of obesity and cancer, as well as neuroinflammatory and chronic inflammatory diseases. Moreover, as we discuss here, additional studies also indicates that these drugs have immunosuppressive and anti-inflammatory properties including modulation of immune cell function. Thus, manipulation of the endocannabinoid system in vivo may provide novel therapeutic strategies against inflammatory disorders. At least two types of cannabinoid receptors, cannabinoid 1 and cannabinoid 2 receptors are expressed on immune cells such as dendritic cells (DC). Dendritic cells are recognized for their critical role in initiating and maintaining immune responses. Therefore, DC are potential targets for cannabinoid-mediated modulation. Here, we review the effects of cannabinoids on DC and provide some perspective concerning the therapeutic potential of cannabinoids for the treatment of human diseases involving aberrant inflammatory processes.

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Section: Cannabinoids and Modulation Of Dendritic Cell Functionmentioning

confidence: 98%

Dendritic Cell Regulation by Cannabinoid-Based Drugs

2010

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“…(a) by down‐regulating macrophage contact‐dependent cytolysis of tumor cells [92]; and (b) by altering both antigen processing [93] and the expression of select macrophage‐associated proteins [94,95]. Incubation of P388D1 macrophage cells in culture with cannabinoids resulted in a dose‐dependent inhibition of cell propagation, DNA synthesis and phagocytosis [96,97]. In humans, cannabinoids inhibited peripheral blood macrophage spreading and phagocytosis [98].…”

Section: Role Of Endocannabinoids In the Modulation Of Immune Responsesmentioning

confidence: 99%

Comparative biology of the endocannabinoid system

Breton

Bisogno

Marzo

2000

European Journal of Biochemistry

116

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In this review we discuss data showing that the endogenous cannabinoid system, represented by cannabinoid receptors, endogenous cannabinoid receptor ligands and enzymes for the biosynthesis and degradation of these ligands, is conserved throughout evolution from coelenterates to man. This signaling system has been suggested to play several roles in animals, including the regulation of cell development and growth, nervous functions, reproduction and feeding behavior. In this article, however, we shall describe with more detail the possible function of the endogenous cannabinoid system in the modulation of immune response in organisms from the lower to the higher levels of animal evolution.Keywords: cannabinoids; anandamide; 2-arachidonoylglycerol; immune response; nitric oxide; invertebrates.Over the past years, numerous studies have demonstrated that some signaling molecules and their corresponding receptors, such as the endorphins and the opiate receptors, have been conserved during evolution [1,2]. Moreover, comparative studies on other chemical signals, such as the eicosanoids, i.e. the derivatives of arachidonic acid, have provided new experimental models for the understanding of the physiological role played by these substances in mammals [3]. In this article, we review recent data on the possible occurrence and biological function in several animal phyla of the newly discovered endogenous cannabinoid system', and, in particular, we describe the possible role of this signaling system in animal immunity. A B R I E F D E S C R I P T I O N O F T H E S T R U C T U R E , B I O S Y N T H E S I S , A C T I O N A N D I N A C T I V A T I O N O F E N D O C A N N A B I N O I D S I N M A M M A L SIn the mammalian brain, the`central' receptor for psychotropic cannabinoids, named CB 1 , was cloned and sequenced in 1990 [4]. Evidence for a second subtype of cannabinoid receptor, named CB 2 was provided in 1993. This latter receptor was almost uniquely expressed in immune cells [5]. At almost the same time, endogenous ligands for these receptors, capable of mimicking to some extent the pharmacological actions of marijuana's psychoactive principle D 9 -tetrahydrocannabinol (THC, Fig. 1), have been discovered. The most representative of these substances, named`endocannabinoids' by analogy with the endorphins, are anandamide (N-arachidonoylethanolamine) and 2-arachidonoylglycerol (2-AG) [6±10]. Although differences between the biological actions of THC or synthetic cannabinoids and their endogenous counterparts have been described, several studies suggest that anandamide and 2-AG act as endogenous agonists of CB 1 and/or CB 2 receptors, thereby mimicking several of the pharmacological and behavioral actions associated with cannabinoids [6±10].Thus, for example, both synthetic cannabinoids and anandamide have neuromodulatory effects [7] through which they influence motor behavior, memory and learning, and sensory, autonomic and neuroendocrine responses. Endocannabinoids also affect reproductive functions and embryo development...

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“…Incubating P388D1 macrophage cell cultures with THC results in a dose-dependent inhibition of cell propagation, DNA synthesis, and phagocytosis (24). In earlier reports, THC was found to inhibit human peripheral blood macrophage spreading and phagocytosis of yeast (25)(26)(27).…”

Section: Figmentioning

confidence: 99%

Cannabinoid Receptors Are Coupled to Nitric Oxide Release in Invertebrate Immunocytes, Microglia, and Human Monocytes

Stefano

Liu

Goligorsky

1996

Journal of Biological Chemistry

175

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The present study demonstrates that stereoselective binding sites for anandamide, a naturally occurring cannabinoid substance, can be found in invertebrate immunocytes and microglia. The anandamide-binding site is monophasic and of high affinity, exhibiting a K d of 34.3 nM with a B max of 441 fmol/mg protein. These sites are highly selective, as demonstrated by the inability of other types of signaling molecules to displace [ 3 H]anandamide. Furthermore, this binding site is coupled to nitric oxide release in the invertebrate tissues examined as well as in human monocytes. Interestingly, the cannabinoid-stimulated release of nitric oxide initiates cell rounding. Thus, these cannabinoid actions resemble those of opiate alkaloids. In this regard, we demonstrate that these signaling systems use the same effector system, i.e. nitric oxide release, but separate receptors. Last, the presence of a cannabinoid receptor in selected evolutionary diverse organisms indicates that this signaling system has been conserved for more than 500 million years. ␦-9-Tetrahydrocannabinol (THC)1 is the active ingredient of marijuana (1). In 1988 a receptor for this substance was identified in the rat brain (2) and subsequently cloned (3). An arachidonic acid derivative, anandamide (N-arachidonoyl-ethanolamine), was later identified as the endogenous ligand for this receptor (4). Extracellular anandamide is rapidly and selectively taken up in neurons, where its degradation to ethanolamine and arachidonate takes place (5). Thus, in a relatively short period of time, a great deal of information has been obtained on cannabinoid receptors and their ligands in mammals.In this regard, it was of interest to determine if cannabinoidbinding sites are found in invertebrates. The present report demonstrates the existance of such a cannabinoid system for the first time.[ 3 H]Anandamide-binding sites are found in Mytilus edulis immunocytes and pedal ganglia microglia membrane homogenates. Furthermore, these high affinity sites appear to be coupled to NO release. Thus, both cannabinoids and opiates share the same effector system by engaging distinct receptors (6, 7). MATERIALS AND METHODSM. edulis, a marine bivalve mollusk, were harvested from Long Island Sound at Montauk and maintained in the laboratory for 3 weeks prior to dissection (9). Invertebrate immunocytes and microglia were collected and processed as described elsewhere in detail (7,10,11).Analysis of Anandamide Binding-Immunocytes ( 10 7 ) were homogenized in 50 volume of 0.32 M sucrose, pH 7.4, at 4°C by the use of a Brinkmann Instruments Polytron (30 s, setting 5). The crude homogenate was centrifuged at 900 ϫ g for 10 min at 4°C, and the supernatant was preserved on ice. The whitish crude pellet was resuspended after homogenization (15 s, setting 5) in 30 volume of 0.32 M sucrose/Tris-HCl buffer, pH 7.4, and centrifuged at 900 ϫ g for 10 min. The extraction procedure was repeated one more time, and the combined supernatants were centrifuged at 900 ϫ g for 10 min. The resulting supern...

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Suppressive Effect of 9-Tetrahydrocannabinol in Vitro on Phagocytosis by Murine Macrophages

Cited by 25 publications

References 0 publications

Dendritic Cell Regulation by Cannabinoid-Based Drugs

Dendritic Cell Regulation by Cannabinoid-Based Drugs

Comparative biology of the endocannabinoid system

Cannabinoid Receptors Are Coupled to Nitric Oxide Release in Invertebrate Immunocytes, Microglia, and Human Monocytes

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