In vivo-transmigrated human neutrophils are resistant to antiapoptotic stimulation
In vivo-transmigrated human neutrophils are resistant to antiapoptotic stimulation
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DOI：
10.1189/jlb.0111051
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发表时间：
2011-12-01
影响因子：
5.5
通讯作者：
Bylund, Johan
中科院分区：
文献类型：
--
作者：
Christenson, Karin;Bjorkman, Lena;Bylund, Johan
中性粒细胞通过从血液到组织的迁移来应对微生物的入侵或损伤。转运涉及细胞活化和脱颗粒，导致表面受体水平的改变和对某些刺激的反应性改变。因此，基本的功能变化与中性粒细胞从血液到组织的迁移有关。从外周血中分离的中性粒细胞自发地进入细胞凋亡，这一过程可以被不同的促凋亡或抗凋亡因子加速或延迟。在体内迁移的组织中性粒细胞如何调节细胞死亡尚不清楚。在这项研究中，使用皮肤室技术收集了体内迁移的中性粒细胞（组织中性粒细胞），并将其与来自同一供者的血液中性粒细胞进行了比较，以了解细胞死亡的调节。皮肤腔液含有多种已知能激活中性粒细胞并调节其寿命的细胞因子。新鲜制备的组织中性粒细胞caspase 3/7活性升高，但具有完全活性；体外培养后的自发性细胞死亡在血液和组织中性粒细胞之间也相似。尽管可溶性抗凋亡因子（如TLR配体）延迟了培养的血液中性粒细胞的凋亡，但组织中性粒细胞完全抵抗抗凋亡刺激，即使受体存在并起作用。在体外，血液中性粒细胞迁移到皮肤腔液中并不能完全抵抗抗凋亡刺激，这表明在体内迁移过程中特异性地发生了抗凋亡信号的阻断。我们描述了一种新的，功能性的改变，发生在体内的转体，并强调了中性粒细胞的生与死可能在血液和组织中受到不同的调节。j . Leukoc。生物学报。90:1055-1063；2011.
Neutrophils respond to microbial invasion or injury by transmigration from blood to tissue. Transmigration involves cellular activation and degranulation, resulting in altered levels of surface receptors and changed responsiveness to certain stimuli. Thus, fundamental functional changes are associated with neutrophil transmigration from blood to tissue. Neutrophils isolated from peripheral blood spontaneously enter apoptosis, a process that can be accelerated or delayed by different pro- or antiapoptotic factors. How tissue neutrophils that have transmigrated in vivo regulate cell death is poorly understood. In this study, in vivo-transmigrated neutrophils (tissue neutrophils) were collected using a skin chamber technique and compared with blood neutrophils from the same donors with respect to regulation of cell death. Skin chamber fluid contained a variety of cytokines known to activate neutrophils and regulate their lifespan. Freshly prepared tissue neutrophils had elevated activity of caspase 3/7 but were fully viable; spontaneous cell death after in vitro culture was also similar between blood and tissue neutrophils. Whereas apoptosis of cultured blood neutrophils was delayed by soluble antiapoptotic factors (e. g., TLR ligands), tissue neutrophils were completely resistant to antiapoptotic stimulation, even though receptors were present and functional. In vitro transmigration of blood neutrophils into skin chamber fluid did not fully confer resistance to antiapoptotic stimulation, indicating that a block of antiapoptotic signaling occurs specifically during in vivo transmigration. We describe a novel, functional alteration that takes place during in vivo transmigration and highlights the fact that life and death of neutrophils may be regulated differently in blood and tissue. J. Leukoc. Biol. 90: 1055-1063; 2011.