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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 CB1 and CB2 receptors, and one of the enzymes mostly responsible for endocannabinoid hydrolysis, the fatty acid amide hydrolase (FAAH) | Eur. J. Biochem. 269 3771-3778 2002 FEBS 2002 doi 10.1046 j.1432-1033.2002.03078.x Presence and regulation of the endocannabinoid system in human dendritic cells Isabel Matias1 Pierre Pochard2 Pieranaelo Orlando3 Michel Salzet4 Joel Pestel2 and Vincenzo Di Marzo1 1 Endocannabinoid Research Group 1Istituto di Chimica Biomolecolare Consiglio Nazionale delle Ricerche Comprensorio Olivetti Pozzuoli Napoli Italy 2Inflammatory Raaciion ad Allergic disaases Department N diCttl untt Pasteur Institute Lille France ĩIstituto di Biochimica delle Proteine ed Enzimologia Consiglio Nazionale delle Ricerche Comprensorio Olivetti Pozzuoli Napoli Italy 4Laboratoire de Nsuroimmunite des Annelides UMR 8017 CNRS Universite des Sciences et Technologies de Lille Villeneuve d Ascq France 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 CB1 and CB2 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 piiiol-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 is sf t ictivel_v . By using both RT-PCR and Western immunoblotting .