Institute of Infection, Inflammation & Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, UK.
FEBS J. 2018 Aug;285(16):2944-2971. doi: 10.1111/febs.14466. Epub 2018 Apr 24.
The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post-translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical 'atypical' chemokine receptors that regulate chemokine localization and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarizes the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focusing particularly on their ability to direct leukocyte migration.
趋化因子(或趋化细胞因子)是一大类小分子分泌蛋白,通过细胞表面 G 蛋白偶联的七螺旋趋化因子受体信号转导。它们最著名的作用是刺激细胞迁移,尤其是白细胞(白细胞)。因此,趋化因子在免疫系统的发育和稳态中起着核心作用,并参与所有保护性或破坏性的免疫和炎症反应。趋化因子经典地被认为是定向趋化迁移的诱导剂,但现在很明显,除了诱导细胞停滞或黏附外,趋化因子还可以刺激各种其他类型的定向和非定向迁移行为,如趋化性、趋化运动和趋化运动。然而,白细胞上的趋化因子受体不仅可以定向迁移,这些分子也可以在许多非白细胞细胞类型上表达,并调节它们的生物学特性。趋化因子受翻译后修饰、与细胞外基质(ECM)相互作用以及与调节趋化因子定位和丰度的七螺旋“非典型”趋化因子受体的结合的深刻影响。本指南广泛概述了趋化因子和趋化因子受体家族;总结了趋化因子网络中发生的复杂物理相互作用;并使用具体示例讨论了趋化因子功能的一般原则,特别关注它们指导白细胞迁移的能力。