EXPRESSION OF CENTRAL AND PERIPHERAL CANNABINOID RECEPTORS IN HUMAN IMMUNE TISSUES AND LEUKOCYTE SUBPOPULATIONS
EXPRESSION OF CENTRAL AND PERIPHERAL CANNABINOID RECEPTORS IN HUMAN IMMUNE TISSUES AND LEUKOCYTE SUBPOPULATIONS
复制标题
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
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发表时间：
1995-08-15
期刊：
影响因子：
--
通讯作者：
CASELLAS, P
中科院分区：
文献类型：
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作者：
GALIEGUE, S;MARY, S;CASELLAS, P
有两种具有典型的鸟苷核苷酸结合蛋白偶联受体的具有七个跨膜结构域的蛋白质被鉴定为大麻素受体；中枢大麻素受体CB1和外周大麻素受体CB2最初分别在大鼠脑和脾中被描述。在这里，我们报告了CB1和CB2转录本在人类免疫细胞和几个人类组织中的分布模式，并使用基于高灵敏度和定量的PCR方法进行了分析。CB1主要表达于中枢神经系统，少量表达于肾上腺、心脏、肺、前列腺、子宫、卵巢、睾丸、骨髓、胸腺和扁桃体等外周组织。相比之下，在大脑中不表达的CB2基因在免疫组织中尤其丰富，其表达水平是CB1的10-100倍。尽管在其他一些外周组织中也检测到CB2mRNA，但其水平仍然很低。在脾和扁桃体中，CB2mRNA的含量与中枢神经系统中的CB1mRNA的含量相当。在人类主要血细胞亚群中，CB2mRNA的分布模式显示出重要的变异。这些细胞中CB2基因的表达顺序为B细胞和自然杀伤细胞，远大于单核细胞和中性粒细胞、T8细胞和T4细胞。在属于髓系、单核细胞系和淋巴系的人类细胞系中也建立了相同的等级顺序。Northern-Blot分析证实了CB2基因在免疫组织中的普遍表达。此外，用特异性抗人CB2抗体对扁桃体切片进行免疫组织学分析，证明了CB2蛋白的表达；本实验表明，CB2的表达仅限于次级淋巴滤泡外套层中B淋巴细胞丰富的区域。这些结果表明，(A)CB1和CB2可分别被认为是中枢神经系统和免疫系统的组织选择性抗原，以及(B)大麻类化合物可能通过CB2受体对免疫系统发挥特异性的受体介导的作用。
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 much greater than 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.