Area of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Munich, Germany.
Eur J Clin Invest. 2018 Nov;48 Suppl 2:e12940. doi: 10.1111/eci.12940. Epub 2018 May 13.
Vascular inflammation underlies most forms of cardiovascular disease, which remains a prevalent cause of death among the global population. Advances in the biology of neutrophils, as well as insights into their dynamics in tissues, have revealed that these cells are prominent drivers of vascular inflammation though derailed activation within blood vessels. The development of powerful imaging techniques, as well as identification of cells and molecules that regulate their activation within vessels, including platelets and catecholamines, has been instrumental to better understand the mechanisms through which neutrophils protect or damage the organism. Other advances in our understanding of how these leucocytes exert detrimental functions on neighbouring cells, including the formation of DNA-based extracellular traps, constitute milestones in defining neutrophil-driven inflammation. Here, we review emerging mechanisms that regulate intravascular activation and effector functions of neutrophils, and discuss specific pathologies in which these processes are relevant. We argue that identification of pathways and mechanisms specifically engaged within the vasculature may provide effective therapies to treat this prevalent group of pathologies.
血管炎症是大多数心血管疾病的基础,它仍然是全球人口死亡的主要原因。中性粒细胞生物学的进展,以及对其在组织中动态的深入了解,揭示了这些细胞是血管炎症的主要驱动因素,尽管它们在血管内的激活是脱轨的。强大的成像技术的发展,以及对调节其在血管内激活的细胞和分子(包括血小板和儿茶酚胺)的鉴定,对于更好地理解中性粒细胞保护或损害机体的机制至关重要。我们对这些白细胞如何对邻近细胞产生有害功能的理解的其他进展,包括基于 DNA 的细胞外陷阱的形成,构成了定义中性粒细胞驱动的炎症的里程碑。在这里,我们综述了调节血管内中性粒细胞激活和效应功能的新机制,并讨论了这些过程相关的特定病理学。我们认为,确定血管内特定参与的途径和机制可能为治疗这一普遍存在的病理学群体提供有效的治疗方法。