EXPRESSION OF CENTRAL AND PERIPHERAL CANNABINOID RECEPTORS IN HUMAN IMMUNE TISSUES AND LEUKOCYTE SUBPOPULATIONS

Two proteins with seven transmembrane-spanning domains typical of guan osine-nucleotide-binding-protein-coupled receptors have been identifie d as cannabinoid receptors; the central cannabinoid receptor, CB1, and the peripheral cannabinoid receptor, CB2, initially described in rat brain and spleen, respectively. Here, we report the distribution patte rns for both CB1 and CB2 transcripts in human immune cells and in seve ral human tissues, as analysed using a highly sensitive and quantitati ve PCR-based method. CB1 was mainly expressed in the central nervous s ystem and, to a lower extent, in several peripheral tissues such as ad renal gland, heart, lung, prostate, uterus, ovary, testis, bone marrow , thymus and tonsils. In contrast, the CB2 gene, which is not expresse d in the brain, was particularly abundant in immune tissues, with an e xpression level 10-100-fold higher than that of CB1. Although CB2 mRNA was also detected in some other peripheral tissues, its level remaine d very low. In spleen and tonsils, the CB2 mRNA content was equivalent to that of CB1 mRNA in the central nervous system. Among the main hum an blood cell subpopulations, the distribution pattern of the CB2 mRNA displayed important variations. The rank order of CB2 mRNA levels in these cells was B-cells > natural killer cells much greater than monoc ytes > polymorphonuclear neutrophil cells > T8 cells > T4 cells. The s ame rank order was also established in human cell lines belonging to t he myeloid, monocytic and lymphoid lineages. The prevailing expression of the CB2 gene in immune tissues was confirmed by Northern-blot anal ysis. In addition, the expression of the CB2 protein was demonstrated by an immunohistological analysis performed on tonsil sections using s pecific anti-(human CB2) IgG; this experiment showed that CB2 expressi on was restricted to B-lymphocyte-enriched areas of the mantle of seco ndary lymphoid follicles. These results suggest that (a) CB1 and CB2 c an be considered as tissue-selective antigens of the central nervous s ystem and immune system, respectively, and (b) cannabinoids may exert specific receptor-mediated actions on the immune system through the CB 2 receptor.