Delayed apoptosis of circulating neutrophils in Kawasaki disease
Delayed apoptosis of circulating neutrophils in Kawasaki disease
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DOI：
10.1046/j.1365-2249.2001.01675.x
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发表时间：
2001-11-01
影响因子：
4.6
通讯作者：
Sekine, I
中科院分区：
文献类型：
--
作者：
Tsujimoto, H;Takeshita, S;Sekine, I
已知循环中的多形核中性粒细胞（PMN）在川崎（KD）的急性期数量增加并且功能性激活。在本研究中，我们调查是否中性粒细胞凋亡失调，在KD。在体外培养中，KD患儿（n = 25）的PMN（Annexin V+细胞和DNA片段化细胞）自发凋亡的比例明显低于细菌感染（n = 20）、病毒感染（n = 20）和健康儿童（n = 20）。川崎病急性期患儿外周血Fas阳性PMN比例明显低于其他各组（P < 0.01）。KD急性期外周血Fas阳性PMN比例与自发凋亡PMN比例呈显著正相关（P < 0.01）。此外，激动性抗Fas单抗（CH-11）诱导病毒感染患者和健康儿童中凋亡的PMN比例显著增加，但在KD患者或细菌感染患者中均未诱导凋亡。在细胞内表达的抗凋亡和促凋亡蛋白，A1/Bax的比例是显着高于在急性KD比其他组。这些研究结果表明，中性粒细胞凋亡的抑制在KD的急性期，也表明，对Fas介导的死亡信号和线粒体凋亡信号通路的下调，由于Bcl-2蛋白表达的平衡改变的阻力是负责延迟中性粒细胞凋亡。
Circulating polymorphonuclear neutrophils (PMNs) are known to increase in number and are functionally activated in the acute phase of Kawasaki disease (KD). In the present study, we investigated whether the apoptosis of PMNs is deregulated in KD. When the isolated PMNs were cultured in vitro, the proportions of spontaneous apoptotic PMNs (annexin V+ cells and cells with fragmented DNA) were found to be significantly lower (P < 0.01) in the patients with KD (n = 25) than in the patients with a bacterial infection (n = 20) or a viral infection (n = 20), or in healthy children (n = 20). The proportion of circulating Fas-positive PMNs was also significantly lower (P < 0.01) in the acute KD patients than in the other groups. In the acute phase of KD, the proportion of spontaneous apoptotic PMNs showed a significant positive correlation (P < 0.01) with the proportions of circulating Fas-positive PMNs. Furthermore, the agonistic anti-Fas MoAb (CH-11) induced a significant increase in the proportion of apoptotic PMNs in the patients with a viral infection and healthy children, but not in either the patients with KD or the patients with a bacterial infection. In the intracellular expression of anti- and pro-apoptotic proteins, the A1/Bax ratio was significantly higher in acute KD than in the other groups. These findings indicate that PMN apoptosis is inhibited during the acute phase of KD and also suggest that both the resistance against the Fas-mediated death signal and the down-regulation of the mitochondrial apoptotic signalling pathway due to an altered balance of Bcl-2 protein expression are responsible for the delayed PMN apoptosis.