Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University Krakow,ul. Ingardena 6, PL-30-060, Poland.
Immunobiology. 2010 Jun;215(6):492-504. doi: 10.1016/j.imbio.2009.07.001. Epub 2009 Aug 4.
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 (6h) 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 (approximately 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.
在炎症期间，粒细胞完成其功能后会在周围组织中通过凋亡程序性死亡，以避免自我组织的破坏。我们旨在研究炎症白细胞凋亡的动力学特征，并验证除了中性粒细胞外，其他炎症白细胞是否也大量发生凋亡。我们观察到，在生理条件下，驻留于腹膜的巨噬细胞或淋巴细胞中凋亡的细胞少于 7%。在急性酵母聚糖诱导的腹膜炎症模型研究中发现，存在两个炎症白细胞凋亡波。第一个波对应于中性粒细胞在腹膜中积累的最大值时间（6 小时），并且凋亡死亡确实主要涉及中性粒细胞（超过 30%的细胞），但此时也有更多的巨噬细胞死亡（>10%）。第二个波（在第 3 天）主要涉及巨噬细胞（20%，而其他群体为 3-6%），与炎症的消退和巨噬细胞的优势存在相一致。相比之下，凋亡的 T（1-3%）和 B（约 5%）细胞的数量在整个腹膜炎期间没有明显变化。两个凋亡波与 caspase-8、-9 和 -3 在转录和活性水平上的增加一致。凋亡诱导因子 TNF-α仅在最初几小时内产生，而一氧化氮则在整个炎症过程中产生。此外，在整个腹膜炎过程中，促凋亡 Bax 的表达超过了抗凋亡 Bcl-2。总之，我们描述了急性腹膜炎症中炎症白细胞凋亡的动力学特征，并揭示了吞噬细胞群体（中性粒细胞和巨噬细胞）在腹膜中大量死亡。
