INSERM U1016, Paris, France.
Institut Cochin, Faculté de Médecine Sorbonne Paris Cité, Université Paris Descartes, Paris, France.
Immunol Rev. 2016 Sep;273(1):344-56. doi: 10.1111/imr.12449.
The life span of a neutrophil is a tightly regulated process as extended survival is beneficial for pathogen elimination and cell death necessary to prevent cytotoxic content release from activated neutrophils at the inflammatory site. Therefore, the control between survival and death must be a dynamic process. We have previously described that proliferating cell nuclear antigen (PCNA) which is known as a nuclear protein pivotal in DNA synthesis, is a key element in controlling neutrophil survival through its association with procaspases. Contrary to the dogma which asserted that PCNA has a strictly nuclear function, in mature neutrophils, PCNA is present exclusively within the cytosol due to its nuclear export at the end of the granulocytic differentiation. More recent studies are consistent with the notion that the cytosolic scaffold of PCNA is aimed at modulating neutrophil fate rather than simply preventing death. Ultimately, targeting neutrophil survival might have important applications not just in the field of immunology and inflammation, but also in hematology and transfusion. The neutrophil emerges as a unique and powerful cellular model to unravel the basic mechanisms governing the cell cycle-independent functions of PCNA and should be considered as a leader of the pack.
中性粒细胞的寿命是一个受到严格调控的过程，因为延长寿命有利于病原体的清除，而细胞死亡对于防止炎症部位激活的中性粒细胞释放细胞毒性物质也是必要的。因此，存活和死亡之间的控制必须是一个动态的过程。我们之前曾描述过，增殖细胞核抗原（PCNA）是一种在 DNA 合成中起关键作用的核蛋白，它通过与前半胱天冬酶的结合成为控制中性粒细胞存活的关键因素。与 PCNA 具有严格核功能的教条相反，在成熟的中性粒细胞中，由于其在粒细胞分化末期从核内输出，PCNA 仅存在于细胞质中。最近的研究结果与这样一种观点一致，即 PCNA 的细胞质支架旨在调节中性粒细胞的命运，而不仅仅是防止其死亡。最终，靶向中性粒细胞的存活可能不仅在免疫学和炎症领域，而且在血液学和输血领域都有重要的应用。中性粒细胞作为一个独特而强大的细胞模型，可以揭示 PCNA 细胞周期非依赖性功能的基本机制，因此应被视为该领域的领导者。
