Pease James Edward, Williams Timothy John
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, South Kensington Campus, Imperial College London, Exhibition Road, London SW7 2AZ.
J Allergy Clin Immunol. 2006 Aug;118(2):305-18; quiz 319-20. doi: 10.1016/j.jaci.2006.06.010.
Mechanisms of chemoattraction underlie the spatial organization of the cells of the immune system under basal conditions and the localization of these cells to sites of inflammation. The chemokines, a family of around 50 small proteins, play a major role in these processes. Leukocytes are equipped with cell-surface sensors for chemokines. There are 19 such receptors that are differentially expressed on leukocytes: the repertoire of receptor expression depending on the type of leukocyte and its stage in maturation. From observations in animal models, clinical studies, in vitro cell biology, and molecular analysis, a working hypothesis has been established to explain the cellular interactions underlying allergic responses and the chemokines-chemokine receptors involved. Chemokines signal through G protein-coupled receptors that are used typically for sensory functions (eg, detection of olfactory signals in the nose). This type of receptor can be blocked selectively by small-molecule antagonists. This provides the opportunity for the development of therapeutic compounds designed to suppress the recruitment of particular leukocyte types in allergic reactions.
趋化作用机制是免疫系统细胞在基础条件下空间组织以及这些细胞在炎症部位定位的基础。趋化因子是一类约50种小蛋白,在这些过程中起主要作用。白细胞配备有趋化因子的细胞表面传感器。有19种这样的受体在白细胞上差异表达:受体表达谱取决于白细胞类型及其成熟阶段。通过对动物模型、临床研究、体外细胞生物学和分子分析的观察,已经建立了一个工作假设,以解释过敏反应背后的细胞相互作用以及所涉及的趋化因子 - 趋化因子受体。趋化因子通过通常用于感觉功能(例如,鼻子中嗅觉信号的检测)的G蛋白偶联受体发出信号。这种类型的受体可以被小分子拮抗剂选择性阻断。这为开发旨在抑制过敏反应中特定白细胞类型募集的治疗化合物提供了机会。