Benarafa Charaf, Simon Hans-Uwe
Theodor Kocher Institute, University of Bern, Bern, Switzerland.
Institute of Pharmacology, University of Bern, Bern, Switzerland.
Biochem Biophys Res Commun. 2017 Jan 15;482(3):473-481. doi: 10.1016/j.bbrc.2016.11.086. Epub 2017 Feb 3.
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression. Neutrophil granules contain abundant amounts of various proteases, which are directly implicated in protective and pathogenic functions of neutrophils. It now emerges that neutral serine proteases such as cathepsin G and proteinase-3 also contribute to the neutrophil life cycle, but do so via different pathways than that of the aspartate protease cathepsin D and that of mutants of the serine protease elastase. The aim of this review is to appraise the present knowledge of the function of neutrophil granule proteases and their inhibitors in neutrophil cell death, and to integrate these findings in the current understandings of neutrophil life cycle and programmed cell death pathways.
中性粒细胞是抵御微生物的固有免疫防御的关键组成部分。中性粒细胞在骨髓中产生并在血管中巡逻，被招募到受损组织后立即发挥作用以遏制病原体入侵。中性粒细胞通过多种特定环境的途径经历程序性细胞死亡，这会对免疫病理学和疾病结局产生影响。过去十年的研究表明，中性粒细胞——或中性粒细胞的一个亚群——在调节适应性反应和肿瘤进展方面具有额外功能。中性粒细胞颗粒含有大量各种蛋白酶，这些蛋白酶直接参与中性粒细胞的保护和致病功能。现在发现，诸如组织蛋白酶G和蛋白酶-3等中性丝氨酸蛋白酶也对中性粒细胞的生命周期有贡献，但它们通过与天冬氨酸蛋白酶组织蛋白酶D和丝氨酸蛋白酶弹性蛋白酶突变体不同的途径发挥作用。本综述的目的是评估目前关于中性粒细胞颗粒蛋白酶及其抑制剂在中性粒细胞细胞死亡中的功能的知识，并将这些发现整合到当前对中性粒细胞生命周期和程序性细胞死亡途径的理解中。
