Expression of functional formyl peptide receptors by human astrocytoma cell lines
Expression of functional formyl peptide receptors by human astrocytoma cell lines
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DOI：
10.1016/s0165-5728(00)00373-8
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发表时间：
2000-11-01
影响因子：
3.3
通讯作者：
Wang, JM
中科院分区：
文献类型：
--
作者：
Le, YY;Hu, JY;Wang, JM
星形胶质细胞的激活在中枢神经系统多种疾病的发病机制中起重要作用，如感染和神经变性。我们发现细菌趋化肽N-甲酰-甲硫基-亮氨酰-苯丙氨酸(FMLF)在人脑星形细胞瘤细胞系中具有较强的迁移和钙离子动员作用。FMLF的作用是百日咳毒素敏感的，提示有7种跨膜G蛋白偶联受体(S)参与FMLF。Scatchard分析表明，星形细胞瘤细胞系同时表达与[H-3]FMLF的高亲和力和低亲和力结合位点。RT-PCR证实这些细胞表达FMLF受体、高亲和力FPRR和低亲和力FPRL1的转录本。FMLF和F肽都能增加星形细胞瘤细胞分泌IL-6的能力。FMLF和F肽是HIV-1包膜蛋白的合成多肽段，可以特异性地激活FPRL1。我们的研究首次证明了星形细胞瘤细胞系表达的FPR和FPRL1具有功能，并提示了这些受体参与脑内宿主防御的分子基础。(C)2000 Elsevier Science B.V.保留所有权利。
Activation of astrocytes is important in the pathogenesis of a variety of diseases in the central nervous system, such as infection and neurodegeneration. We found that the bacterial chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLF) induced potent migration and Ca2+ mobilization in human astrocytoma cell lines. The effect of fMLF was pertussis toxin-sensitive, suggesting the involvement of seven transmembrane, G protein-coupled receptor(s) for fMLF. Scatchard analyses revealed that astrocytoma cell Lines express both high- and low-affinity binding sites for [H-3]fMLF. RT-PCR confirmed the expression of transcripts of fMLF receptors, the high-affinity FPR and the low-affinity FPRL1 by these cells. Both fMLF and F peptide, a synthetic peptide domain of HIV-1 envelope protein which specifically activates FPRL1, increased secretion of IL-6 by astrocytoma cells. Our study demonstrates for the first time that FPR and FPRL1 expressed by astrocytoma cell lines are functional, and suggests a molecular basis for the involvement of these receptors in host defense in the brain. (C) 2000 Elsevier Science B.V. All rights reserved.