Abstract：
In human peripheral blood, the neutrophil granulocytes (neutrophils) are the most-abundant white blood cells. These professional phagocytes are rapidly recruited from the bloodstream to inflamed tissues by chemotactic factors that signal danger. Neutrophils, which express many receptors that are members of the large family of G protein-coupled receptors (GPCRs), are critical for the elimination of pathogens and inflammatory insults, as well as for the resolution of inflammation leading to tissue repair. Danger-signaling molecular patterns such as the N-formylated peptides that are formed during bacterial and mitochondrial protein synthesis and recognized by formyl peptide receptors (FPRs) and free fatty acids recognized by free fatty acid receptors (FFARs) regulate neutrophil functions. Short peptides and short chain fatty acids activate FPR1 and FFA2R, respectively, while longer peptides and fatty acids activate FPR2 and GPR84, respectively. The activation profiles of these receptors include the release of reactive oxygen species (ROS) generated by the NADPH oxidase. Activation of the oxidase and the production of ROS are processes that are regulated by proinflammatory mediators, including TNFα and GM-CSF. The receptors have signaling and functional similarities, although there are also important differences, not only between the two closely related neutrophil FPRs, but also between the FPRs and the FFARs. In neutrophils, these receptors never walk alone, and additional mechanistic insights into the regulation of the GPCRs and the novel regulatory mechanisms underlying the activation of NADPH oxidase advance our understanding of the role of receptor transactivation in the regulation of inflammatory reactions.
摘要：
在人类外周血中，中性粒细胞（嗜中性粒细胞）是最丰富的白细胞。这些专业的吞噬细胞通过信号危险的趋化因子迅速从血液中招募到发炎的组织。中性粒细胞,表达许多受体，这些受体是G蛋白偶联受体（GPCRs）大家族的成员，对消除病原体和炎症至关重要，以及炎症导致组织修复的解决。危险信号传导分子模式，例如在细菌和线粒体蛋白质合成过程中形成并被甲酰肽受体（FPR）识别的N-甲酰化肽和被游离脂肪酸受体（FFAR）识别的游离脂肪酸调节嗜中性粒细胞功能。短肽和短链脂肪酸激活FPR1和FFA2R，分别,而更长的肽和脂肪酸分别激活FPR2和GPR84。这些受体的活化谱包括由NADPH氧化酶产生的活性氧(ROS)的释放。氧化酶的激活和ROS的产生是由促炎介质调节的过程，包括TNFα和GM-CSF。受体具有信号传导和功能相似性，尽管也有重要的区别，不仅在两个密切相关的中性粒细胞FPR之间，而且也在FPR和FFAR之间。在中性粒细胞中，这些受体永远不会独自行走，以及对GPCRs调控的其他机制见解和NADPH氧化酶激活的新调控机制，促进了我们对受体反式激活在炎症反应调控中的作用的理解。
