Beryllium-stimulated reactive oxygen species and macrophage apoptosis
Beryllium-stimulated reactive oxygen species and macrophage apoptosis
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DOI：
10.1016/j.freeradbiomed.2004.12.014
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发表时间：
2005-04-01
影响因子：
7.4
通讯作者：
Day, BJ
中科院分区：
文献类型：
--
作者：
Sawyer, RT;Dobis, DR;Day, BJ
铍（Be）是慢性铍病的病原体，是一种能诱导人肺泡巨噬细胞凋亡的有毒金属。我们测试的假设是，Be刺激活性氧（ROS）的形成，这在Be诱导的巨噬细胞凋亡中发挥作用。小鼠巨噬细胞暴露于100 μ M硫酸铍在催化抗氧化剂MnTBAP（100 μ M）的存在和不存在。细胞凋亡以TUNEL+和caspase-8（+）细胞的百分比来测量。使用荧光探针二氢乙啶（DHE）和二氯荧光素二乙酸酯（DCFH-DA）通过流式细胞术测量ROS产生。暴露于Be的巨噬细胞具有增加的TUNEL+细胞（15 +/-1%对比对照1 +/-0.2%，P < 0.05）和增加的半胱天冬酶-8+细胞（18.7 +/-2%对比对照1.8 +/-0.4%，P < 0.05）。铍诱导的半胱天冬酶-8活化，和4倍增加的ROS形成，改善暴露于MnTBAP。过氧化氢（30 μ M）曝光增强Be诱导的caspase-8激活，也减弱MnTBAP。我们的数据是第一次证明，铍刺激巨噬细胞ROS的形成，这在铍诱导的巨噬细胞凋亡中起着重要作用。(c)2004年爱思唯尔公司All rights reserved.
Beryllium (Be), the etiologic agent of chronic beryllium disease, is a toxic metal that induces apoptosis in human alveolar macrophages. We tested the hypothesis that Be stimulates the formation of reactive oxygen species (ROS) which plays a role in Be-induced macrophage apoptosis. Mouse macrophages were exposed to 100 mu M BeSO4 in the absence and presence of the catalytic antioxidant MnTBAP (100 mu M). Apoptosis was measured as the percentage of TUNEL+ and caspase-8(+) cells. ROS production was measured by flow cytometry using the fluorescence probes, dihydroethidine (DHE) and dichlorofluorescein diacetate (DCFH-DA). Be-exposed macrophages had increased TUNEL+ cells (15 +/- 1% versus controls 1 +/- 0.2%, P < 0.05) and increased caspase-8+ cells (18.7 +/- 2% versus controls 1.8 +/- 0.4%, P < 0.05). Be-induced caspase-8 activation, and a 4-fold increase in ROS formation, was ameliorated by exposure to MnTBAP. Hydrogen peroxide (30 mu M) exposure potentiated Be-induced caspase-8 activation, and was also attenuated by MnTBAP. Our data are the first to demonstrate that Be stimulates macrophage ROS formation which plays an important role in Be-induced macrophage apoptosis. (c) 2004 Elsevier Inc. All rights reserved.