Mechanisms involved in apoptosis of carp leukocytes upon in vitro and in vivo immunostimulation
Mechanisms involved in apoptosis of carp leukocytes upon in vitro and in vivo immunostimulation
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DOI：
10.1016/j.fsi.2014.05.041
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发表时间：
2014-08-01
影响因子：
4.7
通讯作者：
Chadzinska, M.
中科院分区：
文献类型：
--
作者：
Kepka, M.;Verburg-van Kemenade, B. M. L.;Chadzinska, M.
在炎症过程中，必须仔细调节白细胞活性，因为促炎介质例如活性氧（ROS）的高浓度和/或长期作用不仅对病原体而且对宿主组织都是有害的。细胞程序性死亡--凋亡是鱼类白细胞活性下调的最有效的调控机制，但目前对这一过程的研究还不多，本研究旨在揭示鲤鱼嗜中性粒细胞和巨噬细胞凋亡的启动和调控机制，在酵母多糖诱导的鲤鱼腹膜炎过程中，激活的炎症性嗜中性粒细胞和单核/巨噬细胞通过凋亡而死亡。这与一个强大的生产的ROS，但预处理的鱼与NADPH氧化酶抑制剂只略有减少晚期凋亡。有趣的是，在体外培养酵母多糖或佛波酯，但不是脂多糖和poli：C诱导的头肾嗜中性粒细胞凋亡。这与线粒体膜电位的丧失同时发生。此外，在酵母多糖刺激的嗜中性粒细胞中，NADPH氧化酶抑制剂不仅减少ROS的产生，而且还减少凋亡。在用佛波醇酯刺激的细胞中没有观察到类似的效果，其中DPI减少ROS产生，但不减少凋亡。在PMA刺激的嗜中性粒细胞的呼吸爆发和凋亡减少蛋白激酶抑制剂。此外，PMA或酵母多糖短时间刺激中性粒细胞，均能诱导非caspase依赖性的细胞凋亡，表明细胞凋亡是鲤鱼体内外免疫刺激的重要调控过程。在中性粒细胞中，蛋白激酶，而不是NADPH氧化酶，参与PMA诱导的细胞凋亡，而酵母多糖诱导的细胞凋亡是ROS依赖性的。(C)2014爱思唯尔有限公司版权所有。
During inflammation leukocyte activity must be carefully regulated, as high concentrations and/or prolonged action of pro-inflammatory mediators e.g. reactive oxygen species (ROS) can be detrimental not only for pathogens but also for host tissues. Programmed cell death - apoptosis is a most effective regulatory mechanism for down regulation of leukocyte activity, but little is known about this process in fish.We aimed to reveal the mechanisms of initiation and regulation of apoptosis in carp neutrophilic granulocytes and macrophages.During zymosan-induced peritonitis in carp, activated inflammatory neutrophilic granulocytes and monocytes/macrophages died by apoptosis. This correlated with a strong production of ROS, but pre-treatment of the fish with NADPH oxidase inhibitor only slightly decreased late apoptosis. Interestingly in vitro incubation with zymosan or phorbol ester, but not lipopolisaccharide and poli I:C induced apoptosis of head kidney neutrophilic granulocytes. This coincided with loss of mitochondrial membrane potential. Moreover, in zymosan-stimulated neutrophilic granulocytes NADPH oxidase inhibitor not only reduced the production of ROS but also apoptosis. A similar effect was not observed in cells stimulated with phorbol ester, where DPI reduced ROS production, but not apoptosis. In PMA-stimulated neutrophilic granulocytes both the respiratory burst and apoptosis were reduced by protein kinase inhibitor. Furthermore, a short neutrophil stimulation either with PMA or with zymosan did induce caspase-independent apoptosis.These results show that in carp, apoptosis is an important regulatory process during in vitro and in vivo immunostimulation. In neutrophils, protein kinase, but not NADPH oxidase, is involved in PMA-induced apoptosis while apoptosis induced by zymosan is ROS-dependent. (C) 2014 Elsevier Ltd. All rights reserved.