长期乙醇喂养对小鼠树突状细胞数量、更新率和树突形成的影响。
Effects of chronic ethanol feeding on murine dendritic cell numbers, turnover rate, and dendropoiesis.
作者信息
Edsen-Moore Michelle R, Fan Ji, Ness Kristin J, Marietta Jacquie R, Cook Robert T, Schlueter Annette J
机构信息
Department of Pathology, University of Iowa Carver College of Medicine, Iowa 52242, USA.
出版信息
Alcohol Clin Exp Res. 2008 Jul;32(7):1309-20. doi: 10.1111/j.1530-0277.2008.00699.x.
BACKGROUND
Chronic alcoholics have increased susceptibility to and severity of infection, which are likely to be a result of impaired immune defense mechanisms. The contribution of dendritic cells (DC) to these immune defense changes is not well understood. Alterations in DC numbers, dendropoiesis, and lifespan have not been specifically studied in vivo in chronic ethanol (EtOH) exposure models. As DC play an essential role in initiating immune responses, alterations in these DC characteristics would help explain changes observed in adaptive immune responses.
METHODS
Mice received 20% EtOH (w/v) in the drinking water for up to 28 weeks, with mouse chow ad libitum. In EtOH-fed and water control mice, DC were enumerated by flow cytometry. The effect of EtOH on DC precursor numbers was determined by differentiation in vitro in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4, and the effect of an EtOH environment on untreated DC differentiation was measured following bone marrow transfer to irradiated hosts. DC turnover rate was also examined by bromodeoxyuridine incorporation and loss.
RESULTS
The percentage and absolute numbers of DC were decreased in spleen and increased in thymus beginning as early as 4 weeks of EtOH feeding. In addition, the overall cellularity of spleen and thymus were altered by this regimen. However, chronic EtOH consumption did not adversely affect DC precursor numbers, differentiation abilities, or turnover rates.
CONCLUSIONS
Decreased splenic DC numbers observed following chronic murine EtOH consumption are not because of altered DC precursor numbers or differentiation, nor increased DC turnover rate. Similarly, increased thymic DC numbers are not the result of alterations in DC precursor differentiation or turnover rate. Compartment size plays a role in determining splenic and thymic DC numbers following chronic EtOH feeding. EtOH-induced alterations in total DC numbers provide several mechanisms to partially explain why chronic alcoholics have increased susceptibility to infections.
背景
慢性酒精中毒患者对感染的易感性增加且感染严重程度更高，这可能是免疫防御机制受损的结果。树突细胞（DC）对这些免疫防御变化的作用尚未完全明确。在慢性乙醇（EtOH）暴露模型中，尚未在体内专门研究DC数量、树突形成及寿命的改变。由于DC在启动免疫反应中起关键作用，这些DC特性的改变将有助于解释在适应性免疫反应中观察到的变化。
方法
小鼠饮用含20% EtOH（w/v）的水长达28周，自由摄取鼠粮。通过流式细胞术对乙醇喂养小鼠和水对照小鼠的DC进行计数。在粒细胞-巨噬细胞集落刺激因子和白细胞介素-4存在的情况下，通过体外分化确定EtOH对DC前体细胞数量的影响，并在将骨髓移植到受辐照宿主后，测量EtOH环境对未处理的DC分化的影响。还通过溴脱氧尿苷掺入和损失来检测DC更新率。
结果
早在EtOH喂养4周时，脾脏中DC的百分比和绝对数量就开始减少，而胸腺中则增加。此外，该方案改变了脾脏和胸腺的整体细胞数量。然而，慢性EtOH摄入并未对DC前体细胞数量、分化能力或更新率产生不利影响。
结论
慢性小鼠EtOH摄入后脾脏DC数量减少并非由于DC前体细胞数量或分化改变，也不是由于DC更新率增加。同样，胸腺DC数量增加也不是DC前体细胞分化或更新率改变的结果。在慢性EtOH喂养后，隔室大小在决定脾脏和胸腺DC数量方面起作用。EtOH诱导的DC总数改变提供了几种机制，可部分解释为什么慢性酒精中毒患者对感染的易感性增加。
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