Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster, Muenster, Germany.
William Harvey Research Institute, Bart's and the London School of Medicine, Queen Mary University of London, London, United Kingdom; and.
Blood. 2022 Apr 7;139(14):2130-2144. doi: 10.1182/blood.2021012295.
Modulation of neutrophil recruitment and function is crucial for targeting inflammatory cells to sites of infection to combat invading pathogens while, at the same time, limiting host tissue injury or autoimmunity. The underlying mechanisms regulating recruitment of neutrophils, 1 of the most abundant inflammatory cells, have gained increasing interest over the years. The previously described classical recruitment cascade of leukocytes has been extended to include capturing, rolling, adhesion, crawling, and transmigration, as well as a reverse-transmigration step that is crucial for balancing immune defense and control of remote organ endothelial leakage. Current developments in the field emphasize the importance of cellular interplay, tissue environmental cues, circadian rhythmicity, detection of neutrophil phenotypes, differential chemokine sensing, and contribution of distinct signaling components to receptor activation and integrin conformations. The use of therapeutics modulating neutrophil activation responses, as well as mutations causing dysfunctional neutrophil receptors and impaired signaling cascades, have been defined in translational animal models. Human correlates of such mutations result in increased susceptibility to infections or organ damage. This review focuses on current advances in the understanding of the regulation of neutrophil recruitment and functionality and translational implications of current discoveries in the field with a focus on acute inflammation and sepsis.
中性粒细胞募集和功能的调节对于将炎症细胞靶向感染部位以对抗入侵病原体至关重要，同时限制宿主组织损伤或自身免疫。多年来，调节中性粒细胞（最丰富的炎症细胞之一）募集的潜在机制引起了越来越多的关注。先前描述的白细胞经典募集级联已扩展到包括捕获、滚动、黏附、爬行和迁移以及反向迁移步骤，这对于平衡免疫防御和控制远程器官内皮渗漏至关重要。该领域的最新进展强调了细胞相互作用、组织环境线索、昼夜节律性、中性粒细胞表型的检测、趋化因子感应的差异以及不同信号成分对受体激活和整合素构象的贡献的重要性。在转化动物模型中，已经定义了调节中性粒细胞激活反应的治疗方法以及导致功能失调的中性粒细胞受体和受损信号级联的突变。此类突变的人类相关性导致感染或器官损伤的易感性增加。这篇综述重点介绍了对中性粒细胞募集和功能调节的理解的最新进展，以及该领域当前发现的转化意义，重点关注急性炎症和败血症。
