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Inhibitors of CXC chemokine receptor type 4: putative therapeutic approaches in inflammatory diseases

Hummel, Stephaniea,b; Van Aken, Hugoa; Zarbock, Alexandera,b

Current Opinion in Hematology: January 2014 - Volume 21 - Issue 1 - p 29–36
doi: 10.1097/MOH.0000000000000002
MYELOID BIOLOGY: Edited by David C. Dale

Purpose of review: The CXC chemokine receptor type 4 (CXCR4), which is a G-protein coupled receptor, and its ligand CXCL12 play an important role in neutrophil homeostasis and inflammation. This review focuses on involvement of the CXCL12/CXCR4 axis in inflammation and different inflammatory diseases and depicts that blocking CXCR4 is an attractive therapeutic strategy.

Recent findings: Binding of CXCL12 to CXCR4 retains immature neutrophils in the bone marrow and also participates in leukocyte recruitment into inflamed tissue. The CXCL12/CXCR4 axis is also involved in several inflammatory processes and diseases including the WHIM (warts, hypogammaglobulinemia, infections and myelokathexis) syndrome, HIV, autoimmune disorders, ischemic injury, and pulmonary fibrosis.

Summary: Based on these findings, blocking CXCR4 seems to be a therapeutic strategy in inflammatory diseases. Several promising CXCR4 antagonists are in different stages of development and clinical trials. Currently, only plerixafor (AMD3100) has been approved for short-term application.

aDepartment of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster

bMax-Plank Institute Muenster, Muenster, Germany

Correspondence to Alexander Zarbock, MD, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany. Tel: +49 251 83 47252; fax: +49 251 88704; e-mail: zarbock@uni-muenster.de

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