Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary.
Int Immunopharmacol. 2013 Nov;17(3):638-50. doi: 10.1016/j.intimp.2013.06.034. Epub 2013 Aug 30.
Neutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca(2+) signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases.
中性粒细胞在宿主防御细菌和真菌感染中发挥着关键作用,但它们的不当激活也会导致自身免疫和炎症性疾病中的组织损伤。中性粒细胞表达大量细胞表面受体,用于识别病原体入侵和炎症环境。这些受体包括 G 蛋白偶联趋化因子和趋化因子受体、Fc 受体、选择素/选择素配体和整合素等粘附受体、各种细胞因子受体以及 Toll 样受体和 C 型凝集素等先天免疫受体。各种细胞表面受体触发非常多样化的信号转导途径,包括异三聚体和单体 G 蛋白的激活、受体诱导和储存操纵的 Ca(2+)信号、蛋白和脂质激酶、衔接蛋白和细胞骨架重排。本文概述了参与中性粒细胞激活的受体以及它们触发的细胞内信号转导过程。这些知识对于理解中性粒细胞如何参与抗菌宿主防御和炎症性组织损伤至关重要,并且可能为中性粒细胞介导的自身免疫或炎症性疾病的药理学治疗提供潜在的靶点。