Neutrophil chemoattractant receptors in health and disease: double-edged swords.,Cellular & Molecular Immunology

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Neutrophil chemoattractant receptors in health and disease: double-edged swords.
Cellular & Molecular Immunology ( IF 21.8 ) Pub Date : 2020-04-01 , DOI: 10.1038/s41423-020-0412-0
Mieke Metzemaekers ₁ , Mieke Gouwy ₁ , Paul Proost ₁

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Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets.

中文翻译：

健康和疾病中的中性粒细胞趋化因子受体：双刃剑。

中性粒细胞是先天免疫系统的一线细胞。这些效应白细胞配备了有趣的抗菌机制，因此显示出很高的细胞毒性潜力。准确的中性粒细胞募集对于抵抗微生物和恢复体内平衡，调节和解决炎症，伤口愈合和组织修复至关重要。但是，在完成适当的效应子功能后，抑制中性粒细胞的活化和浸润对于防止对宿主的损害至关重要。在人类中，趋化因子分子可分为四个生化家族，即趋化脂质，甲酰基肽，补体过敏毒素和趋化因子。它们与中性粒细胞骨髓储存和流出的严格调节以及器官之间的时空中性粒细胞运输密切相关。趋化因子通过激活专用的七螺旋G蛋白偶联受体（GPCR）发挥功能。此外，新出现的证据表明在微调中性粒细胞的迁徙和功能性反应中，不与G蛋白偶联的非典型趋化性受体（ACKR）具有重要作用。趋化性受体的表达水平取决于嗜中性粒细胞的成熟水平和活化状态，对（炎性）环境具有关键的调节作用。在这里，我们概述了中性粒细胞在健康和疾病中表达的趋化因子受体。根据（病理）生理环境，特定的趋化因子受体在不同的嗜中性粒细胞亚群上可能会上调或下调，从而带来有益或有害的后果，

更新日期：2020-04-24

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