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.

Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)

“…Indeed, nothing is known in cancer patients of what the consequences of MDSC attraction and activation to form NETs could be. However, our results further argue in favor of the convenience of pharmacologically inhibiting IL8 as previously carried out in xenografted mouse models and currently in clinical trials with neutralizing antibodies (51) and small drug inhibitors (52).…”

Anti-inflammatory effect of Schinus terebinthifolius Raddi hydroalcoholic extract on neutrophil migration in zymosan-induced arthritis

“…CXCR2 and CXCR1 signaling plays key roles in neutrophil function, especially in chemotaxis, degranulation, phagocytosis and oxidative burst (Boppana et al, 2014). In our RA experimental model, we observed high levels of CXCL1/KC production and a reduction in the levels of this chemokine after oral pretreatment with ST-70.…”

Live Imaging and Gene Expression Analysis in Zebrafish Identifies a Link between Neutrophils and Epithelial to Mesenchymal Transition

“…A large body of work has explored the role of the chemokine (C-X-C motif) receptor 2 (CXCR2) during leukocyte recruitment to sites of inflammation [6], [15]–[19], [21]–[23]. Previous studies, utilizing the zebrafish model system, have shown that Cxcr2 receptor signaling axis is involved in both long-range systemic neutrophil mobilization from hematopoietic tissue as well as local recruitment to infection or purified Cxcl8 (IL-8, a potent Cxcr2 ligand) [17], [18].…”