Expression of Central and Peripheral Cannabinoid Receptors in Human Immune Tissues and Leukocyte Subpopulations

Abstract

Two proteins with seven transmembrane-spanning domains typical of guanosine-nucleotide-bindingprotein-coupled receptors have been identified 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 patterns for both CB1 and CB2 transcripts in human immune cells and in several human tissues, as analysed using a highly sensitive and quantitative PCR-based method. CB1 was mainly expressed in the central nervous system and, to a lower extent, in several peripheral tissues such as adrenal gland, heart, lung, prostate, uterus, ovary, testis, bone marrow, thymus and tonsils. In contrast, the CB2 gene, which is not expressed in the brain, was particularly abundant in immune tissues, with an expression level 10-100-fold higher than that of CB1. Although CB2 mRNA was also detected in some other peripheral tissues, its level remained 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 human 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 S monocytes > polymorphonuclear neutrophil cells > T8 cells > T4 cells. The same rank order was also established in human cell lines belonging to the inyeloid, monocytic and lymphoid lineages. The prevailing expression of the CB2 gene in immune tissues was confirmed by Northern-blot analysis. In addition, the expression of the CB2 protein was demonstrated by an immunohistological analysis performed on tonsil sections using specific anti-(human CB2) IgG; this experiment showed that CB2 expression was restricted to Blymphocyte-enriched areas of the mantle of secondary lymphoid follicles. These results suggest that (a) CB1 and CB2 can be considered as tissue-selective antigens of the central nervous system and immune system, respectively, and (b) cannabinoids may exert specific receptor-mediated actions on the immune system through the CB2 receptor.Keywords: cannabinoid ; cannabinoid receptors (CB1; CB2) ; human immune system ; B cells; natural killer cells.A-9-Tetrahydrocannabinol, the major active component of cannabis, as well as other cannabinoids, are known to exert a wide range of physiological effects such as drowsiness, alterations in cognition and memory, analgesia, orexigenic effects, anti-emetic effects, a decrease in intra-ocular pressure, anti-inflammatory effects and immunosuppression [l]. Many studies have been conducted to decipher the cannabinoid system. First attributed to non-specific cell membrane disruption, the major cannabinoid effects are now thought to be mediated through specific cannabinoid receptors. A guanosine-nucleotide-bindingprotein-coupled receptor of 472 amino-acid residues, CB1, was initially characterized in rat brain [Z] and further cloned both in rat [3] and human [4]. As the expression of the c...

The orphan receptor GPR55 is a novel cannabinoid receptor

“…CB 2 receptor expression is restricted to the periphery, mainly in immune cells with particularly high levels in B cells and natural killer cells (Galiegue et al, 1995) although it has been reported that the CB 2 receptor is expressed in microglia cells of the CNS and in brain stem neuronal cells (Van Sickle et al, 2005).…”

Du cannabis aux agonistes sélectifs du récepteur CB2

“…En effet, les effets psychotropes (euphorie, vertiges, anxiété, sédation, etc. ), ainsi que la dépendance au THC et autres composés addictogènes (nicotine, alcool, cocaïne), ont été essentiellement attribués au CB 1 R [13], alors que de nombreuses propriétés médicinales, en particulier celles liées à la modulation du système immunitaire, sont probablement associées au CB 2 R [14]. Le CB 1 R est abondamment exprimé dans le système nerveux central, et sa densité est particulièrement forte dans l'hippocampe, le cervelet et le striatum [15].…”

“…Le CB 1 R est abondamment exprimé dans le système nerveux central, et sa densité est particulièrement forte dans l'hippocampe, le cervelet et le striatum [15]. Le CB 2 R est présent également dans le système nerveux central [14], mais il est principalement exprimé sur les cellules immunes activées (lymphocytes B et T, macrophages, monocytes, cellules natural killer [NK], etc.) à des concentrations bien plus élevées que le CB 1 R [14].…”

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

“…Within mus, brainstem and bone marrow. Apart from expression in brain, the CB1 receptor is also expressed in the spleen, heart, prostate, uterus, ovary, thymus and testicles [61] . The location of CB2 receptor is more restricted, mainly at the peripheral level (the spleen, pharyngeal amygdales, B lymphocytes and to a lesser extent, monocytes and T lymphocytes) [61] .…”

“…Apart from expression in brain, the CB1 receptor is also expressed in the spleen, heart, prostate, uterus, ovary, thymus and testicles [61] . The location of CB2 receptor is more restricted, mainly at the peripheral level (the spleen, pharyngeal amygdales, B lymphocytes and to a lesser extent, monocytes and T lymphocytes) [61] . Recently, CB2 expression has been demonstrated in activated microglia and also in neurons, but its level is lower than that of CB1 receptor [62][63][64][65] .…”