Ethanol induces apoptosis in human mast cells
Ethanol induces apoptosis in human mast cells
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DOI：
10.1016/j.lfs.2009.09.004
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发表时间：
2009-11-04
期刊：
影响因子：
6.1
通讯作者：
Eklund, K. K.
中科院分区：
文献类型：
--
作者：
Nurmi, K.;Methuen, T.;Eklund, K. K.
目的：酒精滥用与酒精诱导的免疫抑制引起的感染频率增加有关。然而，免疫抑制的确切机制尚不清楚。肥大细胞（MC）属于先天免疫系统，参与对抗细菌和寄生虫的第一道免疫防御。本研究采用人肥大细胞系（HMC）-1细胞、小鼠骨髓源性肥大细胞（mBMMC）和人外周血源性肥大细胞（HuMC）为研究对象，研究了乙醇及其代谢产物乙醛对肥大细胞活性、增殖和凋亡的影响。通过评估[H-3]胸苷掺入细胞DNA和台盼蓝拒染法测定乙醇和乙醛油对肥大细胞增殖的影响。通过使用ELISA和通过使用Tunel分析测量凋亡核小体和caspase-3、-8和-9活性来评估凋亡。抗凋亡蛋白Bcl-2和促凋亡蛋白Bax的表达分别通过RT-PCR和western blot进行分析。关键发现：乙醇，而不是乙醛抑制HMC-1和mBMMC细胞的增殖和活力呈剂量依赖性。MC的凋亡性细胞死亡导致存活率降低。在43 mM（2.5份/千）乙醇存在下观察到HMC-1细胞的显著凋亡。凋亡诱导与caspase-3活性明显增加和caspase-8和9活性中度增加相关。乙醇也转移Bcl-2/Bax的平衡对apoptosis.Significance：乙醇诱导的MC活力的减少可能有助于与乙醇滥用相关的免疫抑制。(C)2009 Elsevier Inc. All rights reserved.
Aims: Alcohol abuse is associated with increased frequency of infections attributed to ethanol-induced immune suppression. The precise mechanism Of immune suppression is however not known. Mast cells (MC) belong to the innate immune system and they have been implicated in the first line of immune defence against bacteria and parasites. Therefore we studied the effects of ethanol and its first metabolite acetaldehyde on mast cell viability, proliferation and apoptosis.Main methods: Human mast cell line (HMC)-1 cells, mouse bone marrow derived mast cells (mBMMC) and human peripheral blood derived mast cells (HuMC) were used. Effects of ethanol and acetaldehyde oil mast cell proliferation were determined by assessing incorporation of [H-3]thymidine into cellular DNA and by trypan blue exclusion. Apoptosis was assessed by Measuring apoptotic nucleosomes and caspase-3, -8 and -9 activities using ELISA and by using Tunel assay. The expression of anti- and proapoptotic proteins Bcl-2 and Bax was analyzed by RT-PCR and western blot, respectively.Key findings: Ethanol, but not acetaldehyde inhibited dose-dependently the proliferation and viability HMC-1 and mBMMC cells. The decreased viability was caused by apoptotic cell death of the MC. Significant apoptosis of HMC-1 cells was observed in the presence of 43 mM (2.5 parts per thousand) ethanol. Induction of apoptosis was associated with clearly increased caspase-3 activity and moderately increased caspase-8 and 9 activities. Ethanol also shifted the Bcl-2/Bax balance towards apoptosis.Significance: The ethanol-induced reduction of MC viability could contribute to immunosuppression associated with ethanol abuse. (C) 2009 Elsevier Inc. All rights reserved.