Open AccessPresence and regulation of the endocannabinoid system in human dendritic cells
Author(s) -
Matias Isabel,
Pochard Pierre,
Orlando Pierangelo,
Salzet Michel,
Pestel Joel,
Di Marzo Vincenzo
Publication year - 2002
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1033.2002.03078.x
Subject(s) - anandamide , endocannabinoid system , cannabinoid receptor , fatty acid amide hydrolase , 2 arachidonoylglycerol , cannabinoid , chemistry , immune system , cannabinoid receptor type 2 , dendritic cell , lipopolysaccharide , receptor , microbiology and biotechnology , biochemistry , biology , immunology , antagonist
Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in several blood immune cells, including monocytes/macrophages, basophils and lymphocytes. However, their presence in dendritic cells, which play a key role in the initiation and development of the immune response, has never been investigated. Here we have analyzed human dendritic cells for the presence of the endocannabinoids, anandamide and 2‐arachidonoylglycerol (2‐AG), the cannabinoid CB 1 and CB 2 receptors, and one of the enzymes mostly responsible for endocannabinoid hydrolysis, the fatty acid amide hydrolase (FAAH). By using a very sensitive liquid chromatography‐atmospheric pressure chemical ionization‐mass spectrometric (LC‐APCI‐MS) method, lipids extracted from immature dendritic cells were shown to contain 2‐AG, anandamide and the anti‐inflammatory anandamide congener, N ‐palmitoylethanolamine (PalEtn) (2.1 ± 1.0, 0.14 ± 0.02 and 8.2 ± 3.9 pmol·10 −7 cells, respectively). The amounts of 2‐AG, but not anandamide or PalEtn, were significantly increased following cell maturation induced by bacterial lipopolysaccharide (LPS) or the allergen Der p 1 (2.8‐ and 1.9‐fold, respectively). By using both RT‐PCR and Western immunoblotting, dendritic cells were also found to express measurable amounts of CB 1 and CB 2 receptors and of FAAH. Cell maturation did not consistently modify the expression of these proteins, although in some cell preparations a decrease of the levels of both CB 1 and CB 2 mRNA transcripts was observed after LPS stimulation. These findings demonstrate for the first time that the endogenous cannabinoid system is present in human dendritic cells and can be regulated by cell activation.