title: Blockade of CXCR2 signalling: a potential therapeutic target for preventing neutrophil-mediated inflammatory diseases.
abstract: Polymorphonuclear neutrophils (PMN) play a key role in host innate immune responses by migrating to the sites of inflammation. Furthermore, PMN recruitment also plays a significant role in the pathophysiology of a plethora of inflammatory disorders such as chronic obstructive pulmonary disease (COPD), gram negative sepsis, inflammatory bowel disease (IBD), lung injury, and arthritis. Of note, chemokine-dependent signalling is implicated in the amplification of immune responses by virtue of its role in PMN chemotaxis in most of the inflammatory diseases. It has been clinically established that impediment of PMN recruitment ameliorates disease severity and provides relief in majority of other immune-associated disorders. This review focuses on different novel approaches clinically proven to be effective in blocking chemokine signalling associated with PMN recruitment that includes CXCR2 antagonists, chemokine analogs, anti-CXCR2 monoclonal antibodies, and CXCR2 knock-out models. It also highlights the significance of the utility of nanoparticles in drugs used for blocking migration of PMN to the sites of inflammation.
authors.affiliation: Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: Nithin B
authors.initials: NB
authors.lastname: Boppana
authors.forename: Asokan
authors.initials: A
authors.lastname: Devarajan
authors.forename: Kaliappan
authors.initials: K
authors.lastname: Gopal
authors.forename: Muttiah
authors.initials: M
authors.lastname: Barathan
authors.forename: Sazaly A
authors.initials: SA
authors.lastname: Bakar
authors.forename: Esaki M
authors.initials: EM
authors.lastname: Shankar
authors.forename: Abdul S
authors.initials: AS
authors.lastname: Ebrahim
authors.forename: Shukkur M
authors.initials: SM
authors.lastname: Farooq
mesh_terms: D000818:Animals; D002465:Cell Movement; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D015398:Signal Transduction
chemical_list: D023063:Receptors, Interleukin-8B
keywords: CXCR2 antagonists; Chemokine analogs; PMN; integrins; neutrophil infiltration; selectins; transmigration