MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh Medical School, Edinburgh, UK. sfox1 @ staffmail.ed.ac.uk
J Innate Immun. 2010;2(3):216-27. doi: 10.1159/000284367. Epub 2010 Feb 11.
Neutrophils are the most abundant cell type involved in the innate immune response. They are rapidly recruited to sites of injury or infection where they engulf and kill invading microorganisms. Neutrophil apoptosis, the process of programmed cell death that prevents the release of neutrophil histotoxic contents, is tightly regulated and limits the destructive capacity of neutrophil products to surrounding tissue. The subsequent recognition and phagocytosis of apoptotic cells by phagocytic cells such as macrophages is central to the successful resolution of an inflammatory response and it is increasingly apparent that the dying neutrophil itself exerts an anti-inflammatory effect through modulation of surrounding cell responses, particularly macrophage inflammatory cytokine release. Apoptosis may be delayed, induced or enhanced by micro-organisms dependent on their immune evasion strategies and the health of the host they encounter. There is now an established field of research aimed at understanding the regulation of apoptosis and its potential as a target for therapeutic intervention in inflammatory and infective diseases. This review focuses on the physiological regulation of neutrophil apoptosis with respect to the innate immune system and highlights recent advances in mechanistic understanding of apoptotic pathways and their therapeutic manipulation in appropriate and excessive innate immune responses.
中性粒细胞是参与固有免疫反应的最丰富的细胞类型。它们迅速被招募到损伤或感染部位，吞噬并杀死入侵的微生物。中性粒细胞凋亡是程序性细胞死亡的过程，可防止中性粒细胞组织毒性物质的释放，其受到严格调控，并限制了中性粒细胞产物对周围组织的破坏能力。随后，吞噬细胞（如巨噬细胞）对凋亡细胞的识别和吞噬作用是炎症反应成功解决的核心，越来越明显的是，垂死的中性粒细胞本身通过调节周围细胞的反应，特别是巨噬细胞炎症细胞因子的释放，发挥抗炎作用。微生物可能会根据其免疫逃避策略和遇到的宿主的健康状况，延迟、诱导或增强凋亡。现在已经有一个成熟的研究领域旨在了解凋亡的调节及其作为炎症和感染性疾病治疗干预靶点的潜力。这篇综述重点介绍了中性粒细胞凋亡与固有免疫系统的生理调节，并强调了凋亡途径的机制理解方面的最新进展，以及在适当和过度的固有免疫反应中对其进行治疗干预的方法。
