2-Arachidonoylglycerol enhances the phagocytosis of opsonized zymosan by HL-60 cells differentiated into macrophage-like cells
2-Arachidonoylglycerol enhances the phagocytosis of opsonized zymosan by HL-60 cells differentiated into macrophage-like cells
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DOI：
10.1248/bpb.30.1199
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发表时间：
2007-07-01
影响因子：
2
通讯作者：
Sugiura, Takayuki
中科院分区：
文献类型：
--
作者：
Gokoh, Maiko;Kishimoto, Seishi;Sugiura, Takayuki
2-花生四烯基甘油是大麻素受体(CB1和CB2)的内源性配体。虽然越来越多的证据表明CBI受体在各种神经组织和细胞中发挥着重要的调节作用，但在免疫系统中大量表达的CB2受体的生理作用尚未确定。在这项研究中，我们详细检测了2-花生四烯基甘油对已分化为巨噬细胞样细胞的HL-60细胞吞噬调理酵母多糖的影响。我们发现，加入2-花生四烯基甘油可增强分化的HL-60细胞对调理酵母多糖的吞噬作用。这种作用在1 nm处即可观察到，且随2-花生四烯基甘油浓度的增加而增强。用SR144528或百日咳毒素处理细胞后，2-花生四烯酸甘油的作用消失，表明CB2受体和Gi/o参与了吞噬功能的增强。磷脂酰肌醇3-激酶和细胞外信号调节激酶也被认为是参与的；Wortmannin或PD98059处理细胞后，2-花生四烯酸甘油增强的吞噬作用被取消。这些结果有力地表明，来自刺激的炎症细胞的2-花生四烯基甘油在增强巨噬细胞/单核细胞对入侵微生物的吞噬从而刺激炎症反应和免疫反应方面具有重要作用。
2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). While evidence is accumulating that the CBI receptor plays important regulatory roles in various nervous tissues and cells, the physiological roles of the CB2 receptor, which is abundantly expressed in the immune system, are yet to be determined. In this study, we examined in detail the effect of 2-arachidonoylglycerol on the phagocytosis of opsonized zymosan by HL-60 cells that had differentiated into macrophage-like cells. We found that the addition of 2-arachidonoylglycerol augmented the phagocytosis of opsonized zymosan by the differentiated HL-60 cells. The effect was observed from 1 nm and increased with increasing concentrations of 2-arachidonoylglycerol. Treatment of the cells with SR144528 or pertussis toxin abolished the effect of 2-arachidonoylglycerol, indicating that the CB2 receptor and Gi/o are involved in the augmented phagocytosis. Phosphatidylinositol 3-kinase and extracellular signal-regulated kinase were also suggested to be involved; treatment of the cells with wortmannin or PD98059 abrogated the 2-arachidonoylglycerol-augmented phagocytosis. These results strongly suggest that 2-arachidonoylglycerol, derived from stimulated inflammatory cells, has an important role in augmenting the phagocytosis of invading microorganisms by macrophages/monocytes thereby stimulating inflammatory reactions and immune responses.