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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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