Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P
Sanofi Recherche, Immunopharmacology Department, Montpellier, France.
Eur J Biochem. 1995 Aug 15;232(1):54-61. doi: 10.1111/j.1432-1033.1995.tb20780.x.
Two proteins with seven transmembrane-spanning domains typical of guanosine-nucleotide-binding-protein-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 >> monocytes > polymorphonuclear neutrophil cells > T8 cells > T4 cells. The same rank order was also established in human cell lines belonging to the myeloid, 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 B-lymphocyte-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.
已鉴定出两种具有七个跨膜结构域的蛋白质为大麻素受体，这是鸟苷酸结合蛋白偶联受体的典型特征；分别最初在大鼠脑和脾中描述的中枢大麻素受体CB1和外周大麻素受体CB2。在此，我们报告了使用基于PCR的高灵敏度定量方法分析的人免疫细胞和几种人体组织中CB1和CB2转录本的分布模式。CB1主要在中枢神经系统中表达，在肾上腺、心脏、肺、前列腺、子宫、卵巢、睾丸、骨髓、胸腺和扁桃体等几种外周组织中表达程度较低。相比之下，在脑中不表达的CB2基因在免疫组织中特别丰富，其表达水平比CB1高10 - 100倍。尽管在其他一些外周组织中也检测到了CB2 mRNA，但其水平仍然很低。在脾和扁桃体中，CB2 mRNA含量与中枢神经系统中CB1 mRNA的含量相当。在主要的人血细胞亚群中，CB2 mRNA的分布模式显示出重要差异。这些细胞中CB2 mRNA水平的排序为B细胞>自然杀伤细胞>>单核细胞>多形核中性粒细胞>T8细胞>T4细胞。在属于髓系、单核细胞系和淋巴系的人细胞系中也建立了相同的排序。Northern印迹分析证实了CB2基因在免疫组织中的主要表达。此外，使用特异性抗（人CB2）IgG对扁桃体切片进行免疫组织学分析，证实了CB2蛋白的表达；该实验表明CB2表达仅限于次级淋巴滤泡套层中富含B淋巴细胞的区域。这些结果表明：（a）CB1和CB2可分别被视为中枢神经系统和免疫系统的组织选择性抗原；（b）大麻素可能通过CB2受体对免疫系统发挥特定的受体介导作用。
