2-Arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism
2-Arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism
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DOI：
10.1074/jbc.m301359200
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发表时间：
2003-07-04
影响因子：
4.8
通讯作者：
Sugiura, T
中科院分区：
文献类型：
--
作者：
Kishimoto, S;Gokoh, M;Sugiura, T
2-花生四烯醇甘油是大麻素受体（CB1和CB2）的内源性配体，已被证明在体外和体内表现出多种大麻模拟活性。最近，我们提出2-花生四烯醇甘油是大麻素受体的真正内源性配体，并且两种受体（CB1和CB2）主要是2-花生四烯醇甘油受体。CB1受体被认为参与了神经传递的衰减。另一方面，CB2受体在巨噬细胞等几种类型的白细胞中大量表达，其生理作用尚不清楚。在这项研究中，我们检测了2-花生四烯醇甘油对HL-60细胞分化为巨噬细胞样细胞的运动性的影响。我们发现2-花生四烯醇甘油诱导分化的HL-60细胞迁移。用CB2受体拮抗剂SR144528或百日毒处理细胞可阻断2-花生四烯酰基甘油诱导的迁移，表明CB2受体和G(i)/G(o)参与了2-花生四烯酰基甘油诱导的迁移。一些细胞内信号分子如Rho激酶和丝裂原活化蛋白激酶也被认为参与其中。与2-花生四烯醇甘油相比，另一种内源性大麻素受体配体anandamide未能诱导迁移。2-花生四烯酰基甘油诱导的另外两种巨噬细胞样细胞（U937细胞和THP-1细胞）以及人外周血单核细胞的迁移也被观察到。这些结果强烈表明，2-花生四烯醇甘油通过CB2受体依赖机制诱导巨噬细胞/单核细胞等几种白细胞的迁移，从而刺激炎症反应和免疫反应。
2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2) and has been shown to exhibit a variety of cannabimimetic activities in vitro and in vivo. Recently, we proposed that 2-arachidonoylglycerol is the true endogenous ligand for the cannabinoid receptors, and both receptors (CB1 and CB2) are primarily 2-arachidonoylglycerol receptors. The CB1 receptor is assumed to be involved in the attenuation of neurotransmission. On the other hand, the physiological roles of the CB2 receptor, which is abundantly expressed in several types of leukocytes such as macrophages, still remain unknown. In this study, we examined the effects of 2-arachidonoylglycerol on the motility of HL-60 cells differentiated into macrophage-like cells. We found that 2-arachidonoylglycerol induces the migration of differentiated HL-60 cells. The migration induced by 2-arachidonoylglycerol was blocked by treatment of the cells with either SR144528, a CB2 receptor antagonist, or pertussis toxin, suggesting that the CB2 receptor and G(i)/G(o) are involved in the 2-arachidonoylglycerol-induced migration. Several intracellular signaling molecules such as Rho kinase and mitogen-activated protein kinases were also suggested to be involved. In contrast to 2-arachidonoylglycerol, anandamide, another endogenous cannabinoid receptor ligand, failed to induce the migration. The 2-arachidonoylglycerol-induced migration was also observed for two other types of macrophage-like cells, the U937 cells and THP-1 cells, as well as human peripheral blood monocytes. These results strongly suggest that 2-arachidonoylglycerol induces the migration of several types of leukocytes such as macrophages/monocytes through a CB2 receptor-dependent mechanism thereby stimulating inflammatory reactions and immune responses.