CXCR2--the receptor to hit?
Emigration of leukocytes from the microcirculation into inflammatory tissues is one of the hallmarks of our immune system. However, excessive leukocyte recruitment can disturb the integrity of the organism and aggravate acute and chronic inflammatory diseases. Chemokines are chemoattractant peptides that are used as messengers to direct leukocytes to sites of inflammation. They mediate their effects through G-protein-coupled chemokine receptors on the surface of leukocytes and other, nonhematopoietic cells, where they induce a variety of cell responses including cell activation and transmigration. CXC chemokine receptor 2 (CXCR2) has been implicated in numerous inflammatory disorders. In many models of acute and chronic inflammatory diseases, blockade of CXCR2 substantially reduces leukocyte recruitment, tissue damage and mortality. The physiological importance of CXCR2 has led to the development of selective CXCR2 inhibitors that are now being tested in clinical trials. This review will summarize current knowledge about CXCR2 in inflammatory diseases and discuss its potential as a pharmaceutical target.
Reutershan
Jörg
J
Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. joerg.reutershan@uni-tuebingen.de
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy / Q000503:physiopathology; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002908:Chronic Disease; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011487:Protein Conformation; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000503:physiopathology; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D018925:Chemokines; D023063:Receptors, Interleukin-8B