Inflammatory macrophages, and not only neutrophils, die by apoptosis during acute peritonitis
Inflammatory macrophages, and not only neutrophils, die by apoptosis during acute peritonitis
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DOI：
10.1016/j.imbio.2009.07.001
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发表时间：
2010-06-01
期刊：
影响因子：
2.8
通讯作者：
Arnold, Bernd
中科院分区：
文献类型：
--
作者：
Kolaczkowska, Elzbieta;Koziol, Agnieszka;Arnold, Bernd
中心范式认为，在炎症期间，粒细胞在完成其功能后，外围细胞凋亡，以避免破坏自身组织。在这里，我们旨在研究炎症性白细胞凋亡的动力学方面，并验证除了中性粒细胞外，其他炎症性白细胞是否也大量凋亡。我们观察到，在生理条件下，不到7%的常驻腹膜巨噬细胞或淋巴细胞凋亡。对急性酶促性腹膜炎症模型的研究表明，炎症性白细胞凋亡有两波。第一个波对应于中性粒细胞在腹膜的最大积聚时间（6小时），凋亡性死亡确实主要涉及中性粒细胞（超过30%），但此时也有更多的巨噬细胞死亡（约10%）。第二波（3天）主要涉及巨噬细胞（20%，而其他人群为3-6%），与炎症消退和巨噬细胞的显性存在相吻合。相反，T细胞凋亡（1-3%）和B细胞凋亡（接近5%）的数量在整个腹膜炎期间没有明显变化。这两波凋亡与caspase-8、-9和-3在转录和活性水平上的增加一致。凋亡诱导剂tnf - α仅在第一个小时产生，而一氧化氮则在所有炎症过程中产生。此外，在整个腹膜炎过程中，促凋亡的Bax表达高于抗凋亡的Bcl-2。总之，我们表征了急性腹膜炎症期间炎性白细胞凋亡死亡的动力学，并揭示了腹膜中吞噬细胞群（中性粒细胞和巨噬细胞）大量死亡。2009爱思唯尔有限公司版权所有。
The central paradigm says that during inflammation, after completing their function, granulocytes die apoptotically in periphery to avoid destruction of self-tissues. Here we aimed to investigate the kinetic aspect of inflammatory leukocyte apoptosis and verify whether apart from neutrophils also other inflammatory leukocytes numerously undergo apoptosis. We observed that in physiological conditions, less than 7% of either resident peritoneal macrophages or lymphocytes die apoptotically. The studies on a model of acute zymosan-induced peritoneal inflammation revealed that there are two waves of inflammatory leukocyte apoptosis. The first wave corresponds to the time of maximal neutrophil accumulation in peritoneum (6 h) and the apoptotic death indeed concerns mostly neutrophils (over 30% of those cells), but also more macrophages die at this time (> 10%). The second wave (at 3 days) concerns mostly macrophages (20% versus 3-6% for other populations) and coincides with the resolution of inflammation and the dominant presence of macrophages. In contrast, numbers of apoptotic T (1-3%) and B (similar to 5%) cells do not significantly change during the whole peritonitis. The two waves of apoptosis concur with an increase of caspase-8, -9 and -3 at the transcript and activity levels. The apoptosis inducer TNF-alpha is produced only during first hours while nitric oxide throughout all inflammation. Moreover, during the whole course of peritonitis the expression of pro-apoptotic Bax dominates over anti-apoptotic Bcl-2. In conclusion, we characterized kinetics of apoptotic death of inflammatory leukocytes during acute peritoneal inflammation and revealed that both phagocyte populations (neutrophils and macrophages) die numerously in peritoneum. (C) 2009 Elsevier GmbH. All rights reserved.