Effects of chronic ethanol feeding on murine dendritic cell numbers, turnover rate, and dendropoiesis
Effects of chronic ethanol feeding on murine dendritic cell numbers, turnover rate, and dendropoiesis
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DOI：
10.1111/j.1530-0277.2008.00699.x
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发表时间：
2008-07-01
影响因子：
3.2
通讯作者：
Schlueter, Annette J.
中科院分区：
文献类型：
--
作者：
Edsen-Moore, Michelle R.;Fan, Ji;Schlueter, Annette J.
背景：慢性酗酒者对感染的易感性和严重程度增加，这可能是免疫防御机制受损的结果。树突状细胞(DC)在这些免疫防御变化中的作用尚不清楚。在慢性乙醇(Etoh)暴露模型中，DC数量、树突状细胞的形成和寿命的变化还没有专门在体内进行研究。由于DC在启动免疫反应中起着重要作用，这些DC特性的改变将有助于解释观察到的获得性免疫反应的变化。方法：小鼠在饮用水中加入20%乙醇(w/v)，持续28周，并自由进食。用流式细胞仪对乙醇喂养小鼠和水对照组小鼠的DC进行计数。在粒-巨噬细胞集落刺激因子和白介素4的存在下，通过体外分化检测乙醇对DC前体数量的影响，并在骨髓移植到照射宿主后检测乙醇环境对未经处理的DC分化的影响。结果：乙醇喂养4周后，小鼠脾脏DC百分率和绝对数减少，胸腺DC百分率和绝对数增加。此外，该方案还改变了脾和胸腺的总体细胞密度。结论：慢性摄入乙醇后小鼠脾DC数量减少并不是由于DC前体数量或分化程度的改变，也不是由于DC周转率的增加。同样，胸腺DC数量的增加并不是DC前体分化或周转率改变的结果。隔室大小在决定慢性乙醇喂养后的脾和胸腺树突状细胞数量方面起着作用。乙醇诱导的DC总数的变化提供了几种机制来部分解释为什么慢性酒精中毒患者对感染的易感性增加。
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.