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

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.