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The role of CXCR2 in acute inflammatory responses and its antagonists as anti-inflammatory therapeutics

Zhang, Xiaoyua,b; Guo, Rongxiac; Kambara, Hirotoa,b; Ma, Fengxiac; Luo, Hongbo R.a,b

Current Opinion in Hematology: January 2019 - Volume 26 - Issue 1 - p 28–33
doi: 10.1097/MOH.0000000000000476
MYELOID BIOLOGY: Edited by David C. Dale

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.

aDepartment of Pathology, Harvard Medical School

bDepartment of Lab Medicine, The Stem Cell Program, Boston Children's Hospital, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts, USA

cThe State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China

Correspondence to Hongbo R. Luo, Department of Pathology, Harvard Medical School, Boston, Massachu. setts, USA. Tel: +1 617 919 2303; e-mail: Hongbo.Luo@childrens.harvard.edu

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