Department of Anesthesiology and Intensive Care Medicine, Klinikum Rechts der Isar, Technical University Munich, 81675 Munich, Germany.
Int J Mol Sci. 2021 Dec 27;23(1):275. doi: 10.3390/ijms23010275.
Netrins belong to the family of laminin-like secreted proteins, which guide axonal migration and neuronal growth in the developing central nervous system. Over the last 20 years, it has been established that netrin-1 acts as a chemoattractive or chemorepulsive cue in diverse biological processes far beyond neuronal development. Netrin-1 has been shown to play a central role in cell adhesion, cell migration, proliferation, and cell survival in neuronal and non-neuronal tissue. In this context, netrin-1 was found to orchestrate organogenesis, angiogenesis, tumorigenesis, and inflammation. In inflammation, as in neuronal development, netrin-1 plays a dichotomous role directing the migration of leukocytes, especially monocytes in the inflamed tissue. Monocyte-derived macrophages have long been known for a similar dual role in inflammation. In response to pathogen-induced acute injury, monocytes are rapidly recruited to damaged tissue as the first line of immune defense to phagocyte pathogens, present antigens to initiate the adaptive immune response, and promote wound healing in the resolution phase. On the other hand, dysregulated macrophages with impaired phagocytosis and egress capacity accumulate in chronic inflammation sites and foster the maintenance-and even the progression-of chronic inflammation. In this review article, we will highlight the dichotomous roles of netrin-1 and its impact on acute and chronic inflammation.
神经轴突导向因子 1 属于层粘连蛋白样分泌蛋白家族，在中枢神经系统的发育过程中，它可以引导轴突迁移和神经元生长。在过去的 20 年中，已经确定神经轴突导向因子 1 在神经元发育之外的多种生物学过程中作为化学吸引或化学排斥信号发挥作用。神经轴突导向因子 1 已被证明在神经元和非神经元组织的细胞黏附、细胞迁移、增殖和细胞存活中发挥核心作用。在这种情况下，神经轴突导向因子 1 被发现可以协调器官发生、血管生成、肿瘤发生和炎症。在炎症中，与神经元发育一样，神经轴突导向因子 1 发挥着双重作用，指导白细胞，特别是单核细胞在炎症组织中的迁移。单核细胞衍生的巨噬细胞在炎症中一直具有类似的双重作用。在病原体诱导的急性损伤中，单核细胞作为第一道免疫防御迅速募集到受损组织，吞噬病原体，呈递抗原以启动适应性免疫反应，并在解决阶段促进伤口愈合。另一方面，吞噬作用和迁出能力受损的失调巨噬细胞在慢性炎症部位积累，并促进慢性炎症的维持甚至进展。在这篇综述文章中，我们将重点介绍神经轴突导向因子 1 的双重作用及其对急性和慢性炎症的影响。
