Spontaneous apoptosis in lymphocytes from patients with Wiskott-Aldrich syndrome: correlation of accelerated cell death and attenuated bcl-2 expression.
Spontaneous apoptosis in lymphocytes from patients with Wiskott-Aldrich syndrome: correlation of accelerated cell death and attenuated bcl-2 expression.
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DOI：
10.1182/blood.v94.11.3872
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发表时间：
1999-12
期刊：
影响因子：
20.3
通讯作者：
Stephen L. Rawlings;David Bockstoce;L. Barsky;Robertson Parkman;Kenneth I. Weinberg
中科院分区：
文献类型：
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作者：
Stephen L. Rawlings;David Bockstoce;L. Barsky;Robertson Parkman;Kenneth I. Weinberg
Wiskott-Aldrich综合征（WAS）是一种X连锁隐性遗传疾病，其特征是血小板减少、湿疹和免疫功能进行性恶化。WAS是由细胞内蛋白WASP突变引起的，WASP参与信号转导和肌动蛋白细胞骨架重排的调节。由于免疫功能障碍在WAS可能是由于加速破坏淋巴细胞，我们研究了在没有外源性致凋亡刺激的情况下，从WAS患者分离的静息原代淋巴细胞对凋亡的敏感性。我们发现，未受刺激的WAS淋巴细胞发生自发凋亡的频率比未受刺激的正常淋巴细胞。与凋亡易感性增加一致，WAS淋巴细胞Bcl-2表达明显减弱，而Bax表达没有差异。Bcl-2的表达水平与自发凋亡率呈负相关。这些数据表明，通过自发诱导细胞凋亡加速淋巴细胞破坏可能是WAS患者发生进行性免疫缺陷的一种致病机制。
Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema, and a progressive deterioration of immune function. WAS is caused by mutations in an intracellular protein, WASP, that is involved in signal transduction and regulation of actin cytoskeleton rearrangement. Because immune dysfunction in WAS may be due to an accelerated destruction of lymphocytes, we examined the susceptibility to apoptosis of resting primary lymphocytes isolated from WAS patients in the absence of exogenous apoptogenic stimulation. We found that unstimulated WAS lymphocytes underwent spontaneous apoptosis at a greater frequency than unstimulated normal lymphocytes. Coincident with increased apoptotic susceptibility, WAS lymphocytes had markedly attenuated Bcl-2 expression, whereas Bax expression did not differ. A negative correlation between the frequency of spontaneous apoptosis and the level of Bcl-2 expression was demonstrated. These data indicate that accelerated lymphocyte destruction by spontaneous induction of apoptosis may be one pathogenic mechanism by which the progressive immunodeficiency in WAS patients develops.