CXCR2 在急性炎症反应中的作用及其拮抗剂作为抗炎治疗药物。
The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics.
机构信息
Department of Pathology, Harvard Medical School.
Department of Lab Medicine, The Stem Cell Program, Boston Children's Hospital, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA.
出版信息
Curr Opin Hematol. 2019 Jan;26(1):28-33. doi: 10.1097/MOH.0000000000000476.
PURPOSE OF REVIEW
CXCR2 is key stimulant of immune cell migration and recruitment, especially of neutrophils. Alleviating excessive neutrophil accumulation and infiltration could prevent prolonged tissue damage in inflammatory disorders. This review focuses on recent advances in our understanding of the role of CXCR2 in regulating neutrophil migration and the use of CXCR2 antagonists for therapeutic benefit in inflammatory disorders.
RECENT FINDINGS
Recent studies have provided new insights into how CXCR2 signaling regulates hematopoietic cell mobilization and function in both health and disease. We also summarize several CXCR2 regulatory mechanisms during infection and inflammation such as via Wip1, T-bet, P-selectin glycoprotein ligand-1, granulocyte-colony-stimulating factor, and microbiome. Moreover, we provide an update of studies investigating CXCR2 blockade in the laboratory and in clinical trials.
SUMMARY
Neutrophil homeostasis, migration, and recruitment must be precisely regulated. The CXCR2 signaling pathway is a potential target for modifying neutrophil dynamics in inflammatory disorders. We discuss the recent clinical use of CXCR2 antagonists for controlling inflammation.
目的综述：CXCR2 是免疫细胞迁移和募集的关键刺激物，特别是中性粒细胞。减轻过度的中性粒细胞积累和浸润可能会预防炎症性疾病中的组织损伤延长。本综述重点介绍了我们对 CXCR2 在调节中性粒细胞迁移中的作用的最新理解，以及 CXCR2 拮抗剂在炎症性疾病中的治疗益处。
最新发现：最近的研究提供了新的见解，说明 CXCR2 信号如何调节健康和疾病中造血细胞的动员和功能。我们还总结了感染和炎症期间的几个 CXCR2 调节机制，例如通过 Wip1、T-bet、P 选择素糖蛋白配体-1、粒细胞集落刺激因子和微生物组。此外，我们提供了在实验室和临床试验中研究 CXCR2 阻断的最新情况。
总结：中性粒细胞的动态平衡、迁移和募集必须得到精确的调节。CXCR2 信号通路是调节炎症性疾病中性粒细胞动力学的潜在靶点。我们讨论了最近 CXCR2 拮抗剂在控制炎症中的临床应用。
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