Rapid killing of human neutrophils by the potent activator phorbol 12-myristate 13-acetate (PMA) accompanied by changes different from typical apoptosis or necrosis
Rapid killing of human neutrophils by the potent activator phorbol 12-myristate 13-acetate (PMA) accompanied by changes different from typical apoptosis or necrosis
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DOI：
10.1002/jlb.59.2.229
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发表时间：
1996-02-01
影响因子：
5.5
通讯作者：
Sendo, F
中科院分区：
文献类型：
--
作者：
Takei, H;Araki, A;Sendo, F
为了阐明中性粒细胞激活与其随后死亡之间的关系，检测了中性粒细胞的有效激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)的作用。PMA处理后的中性粒细胞形态变化与典型的细胞凋亡或坏死不同，分叶核融合后，核染色质含量均匀减少，致密，核膜破裂后不久。即使在这个阶段，细胞质细胞器也没有退化。经PMA处理的中性粒细胞DNA常规琼脂糖凝胶电泳法和脉冲场凝胶电泳法均未发现小于300kBP的DNA降解产物，PMA作用3h后，细胞膜通透性开始增加。PKC抑制剂星形孢子素和H-7可阻断PMA的细胞毒作用。此外，抗氧化剂硫脲、二甲基硫脲、二甲基氨基甲酸酯和N-乙酰-L-半胱氨酸对PMA的细胞毒性也有抑制作用，但没有超氧化物歧化酶的作用，提示PMA处理后细胞自杀的原因是氧自由基，尤其是羟基自由基，吞噬调理酵母多糖的一定数量的中性粒细胞也表现出与PMA处理细胞相似的变化。
To elucidate the relationship between activation of neutrophils and their subsequent death, the effect of phorbol 12-myristate 13-acetate (PMA), a potent activator of neutrophils, was examined. PMA-treated neutrophils showed morphological changes quite different from those of typical apoptosis or necrosis, After fusion of the lobate nucleus, nuclear contents of chromatin uniformly decreased in compactness and soon after the nuclear envelope was broken. Even at this stage, cytoplasmic organelles did not undergo degeneration. Membrane permeability began increasing at 3 h of incubation with PMA, subsequent to nuclear change, Conventional agarose gel electrophoresis and pulsed field gel electrophoresis of DNA from PMA-treated neutrophils revealed no DNA degradation products smaller than 300 kbp. PKC inhibitors, staurosporine and H-7, prevented cytotoxicity by PMA. Furthermore, antioxidants, thiourea, dimethylthiourea, pyrrolidimethiocarbamate, and N-acetyl-L-cysteine, but not superoxide dismutase, were also active ill preventing PMA cytotoxicity, suggesting that cell suicide resulting from PMA treatment is due to oxygen radicals, especially the hydroxyl radical, A certain population of neutrophils phagocytosing opsonized zymosan also showed changes similar to those observed in PMA-treated cells.