Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse.
Characterization and function of the human macrophage dopaminergic system: implications for CNS disease and drug abuse.
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DOI：
10.1186/1742-2094-9-203
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发表时间：
2012-08-18
影响因子：
9.3
通讯作者：
Berman JW
中科院分区：
文献类型：
--
作者：
Gaskill PJ;Carvallo L;Eugenin EA;Berman JW
血管周围巨噬细胞和小胶质细胞对中枢神经系统功能至关重要。滥用药物会增加中枢神经系统的细胞外多巴胺，使这些细胞暴露在多巴胺水平升高的环境中。在啮齿动物巨噬细胞和人类t细胞中，多巴胺被证明通过激活多巴胺受体和其他多巴胺能蛋白来调节细胞功能。这些蛋白的表达以及多巴胺对人巨噬细胞功能的影响尚未被研究。为了研究多巴胺能基因的表达，我们对人单核细胞源性巨噬细胞（MDM） mRNA进行了qRT-PCR检测。通过免疫印迹法检测MDM分离的质膜、总膜和胞质蛋白的表达和定位。为了表征多巴胺在基础和炎症条件下介导的细胞因子产生的变化，在LPS存在或不存在的情况下，用不同浓度的多巴胺处理巨噬细胞，并通过ELISA检测细胞因子的产生。采用双尾学生t检验或wilcox sign Rank检验确定统计学显著性。这些数据表明，MDM表达所有5种多巴胺受体亚型的mRNA，并且多巴胺受体3和4在质膜上表达。MDM还表达多巴胺转运蛋白（DAT）、囊泡单胺转运蛋白2 （VMAT2）、酪氨酸羟化酶（TH）和芳香氨基酸脱羧酶（AADC）的mRNA。DAT在质膜上表达，VMAT2在细胞膜上表达，TH和AADC在细胞质溶胶中表达。多巴胺也会改变未处理和lps处理的细胞中巨噬细胞细胞因子的产生。未经治疗的巨噬细胞显示多巴胺介导的IL-6和CCL2升高。LPS处理的巨噬细胞显示IL-6、CCL2、CXCL8和IL-10升高，TNF-α降低。单核细胞来源的巨噬细胞表达多巴胺受体和其他多巴胺能蛋白，多巴胺可能通过这些蛋白调节巨噬细胞的功能。因此，药物滥用导致的中枢神经系统多巴胺水平升高可能加剧包括阿尔茨海默病和HIV相关神经系统疾病在内的神经系统疾病的发展。
Perivascular macrophages and microglia are critical to CNS function. Drugs of abuse increase extracellular dopamine in the CNS, exposing these cells to elevated levels of dopamine. In rodent macrophages and human T-cells, dopamine was shown to modulate cellular functions through activation of dopamine receptors and other dopaminergic proteins. The expression of these proteins and the effects of dopamine on human macrophage functions had not been studied. To study dopaminergic gene expression, qRT-PCR was performed on mRNA from primary human monocyte derived macrophages (MDM). Expression and localization of dopaminergic proteins was examined by immunoblotting isolated plasma membrane, total membrane and cytosolic proteins from MDM. To characterize dopamine-mediated changes in cytokine production in basal and inflammatory conditions, macrophages were treated with different concentrations of dopamine in the presence or absence of LPS and cytokine production was assayed by ELISA. Statistical significance was determined using two-tailed Students’ T-tests or Wilcoxen Signed Rank tests. These data show that MDM express mRNA for all five subtypes of dopamine receptors, and that dopamine receptors 3 and 4 are expressed on the plasma membrane. MDM also express mRNA for the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC). DAT is expressed on the plasma membrane, VMAT2 on cellular membranes and TH and AADC are in the cytosol. Dopamine also alters macrophage cytokine production in both untreated and LPS-treated cells. Untreated macrophages show dopamine mediated increases IL-6 and CCL2. Macrophages treated with LPS show increased IL-6, CCL2, CXCL8 and IL-10 and decreased TNF-α. Monocyte derived macrophages express dopamine receptors and other dopaminergic proteins through which dopamine may modulate macrophage functions. Thus, increased CNS dopamine levels due to drug abuse may exacerbate the development of neurological diseases including Alzheimer’s disease and HIV associated neurological disorders.
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影响因子：
3.3
作者：
GONON, FG;BUDA, MJ
通讯作者：
BUDA, MJ
影响因子：
15.1
作者：
Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
通讯作者：
Tansey MG
影响因子：
3.9
作者：
Alberio, Tiziana;Anchieri, Claudia;Fasano, Mauro
通讯作者：
Fasano, Mauro
影响因子：
6.1
作者：
Cosentino, M;Bombelli, R;Frigo, G
通讯作者：
Frigo, G
影响因子：
5.3
作者：
Eugenin, EA;Osiecki, K;Berman, JW
通讯作者：
Berman, JW