The functional significance behind expressing two IL–8 receptor types on PMN

Abstract

PMN are critical to innate immunity and are fundamental to antibacterial defense. To localize to sites of infection, PMN possess receptors that detect chemoattractant stimuli elicited at the site, such as chemokines, complement split products, or bioactive lipids. Signaling through these receptors stimulates chemotaxis toward the site of infection but also activates a number of biochemical processes, with the result that PMN kill invading bacteria. PMN possess two receptors, CXCR1 and CXCR2, for the N-terminal ELR motif-containing CXC chemokines, although only two chemokine members bind both receptors and the remainder binding only CXCR2. This peculiar pattern in receptor specificity has drawn considerable interest and investigation into whether signaling through each receptor might impart unique properties on the PMN. Indeed, at first glance, CXCR1 and CXCR2 appear to be functionally redundant; however, there are differences. Considering these proinflammatory activities of activating PMN through chemokine receptors, there has been great interest in the possibility that blocking CXCR1 and CXCR2 on PMN will provide a therapeutic benefit. The literature examining CXCR1 and CXCR2 in PMN function during human and modeled diseases will be reviewed, asking whether the functional differences can be perceived based on alterations in the role PMN play in these processes.

G31P, an Antagonist against CXC Chemokine Receptors 1 and 2, Inhibits Growth of Human Prostate Cancer Cells in Nude Mice

“…In addition, VEGF is a NF-κB-inducible protein that is the most specific and potent angiogenic factor in tumor-induced angiogenesis. A number of studies have demonstrated that the metastatic potential of tumor cells is associated with VEGF overexpression through activation of the NF-κB pathway (Stillie et al 2009). In the current study, we demonstrated that G31P treatment suppressed the expression of both VEGF and NF-κB in tumor xenograft tissues.…”

Pseudogout-Associated Inflammatory Calcium Pyrophosphate Dihydrate Microcrystals Induce Formation of Neutrophil Extracellular Traps

“…8D). IL-8 is a potent chemoattractant for neutrophils, and one of its main receptors is CXCR2 (52). To study whether IL-8 release and recruitment of neutrophils through CXCR2 binding plays a role in CPPD-induced NET formation, we exposed attached neutrophils to CPPD crystals in the presence of the specific CXCR2 inhibitor SB225002 (53).…”

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells

“…Neutralization of both receptors together did not have additive effects, suggesting a co-dependency of receptor function by heterodimerization, as earlier reviewed in ref. 20. CXCR1 and CXCR2 are known to be internalized on ligand activation 21 , which initiates CXCL8 signalling 22 .…”