C-X-C chemokine receptor type 1 (CXCR1) and C-X-C chemokine receptor type 2 (CXCR2) (CXCR1 (for C-X-C chemokine receptor type 1), CXCR2 (for C-X-C chemokine receptor type 2))

C-X-C chemokine receptor type 1 (CXCR1) and type 2 (CXCR2) are closely related G protein-coupled receptors that primarily bind ELR+ CXC chemokines, especially CXCL8 (interleukin-8), and mediate neutrophil chemotaxis, activation, and inflammatory responses. They are seven-transmembrane proteins expressed mainly on neutrophils but also on other leukocyte subtypes, endothelial cells, and some tumor cells. CXCR2 responds to a broader spectrum of chemokines, while CXCR1 is more selective for CXCL8 and CXCL6 and is chiefly responsible for oxidative burst and NET formation. Both play key roles in immune cell trafficking, host defense against infections, and are implicated in pathological processes such as chronic inflammation, autoimmune disease, tumor progression, angiogenesis, and bone marrow fibrosis. Several small-molecule inhibitors of CXCR1/2 are under clinical and preclinical investigation for these and related diseases. CXCR1 and CXCR2 have considerable sequence homology but differ in ligand specificity, recycling kinetics, and some downstream signaling pathways. Their clinical targeting is promising but care must be taken due to risks of increased susceptibility to infections and impaired tissue repair.

Other names

Interleukin-8 receptor alpha (IL8RA, for CXCR1)Interleukin-8 receptor beta (IL8RB, for CXCR2)IL-8RCD181 (CXCR1)CD182 (CXCR2)

Antagonists block ligand (mainly CXCL8/IL-8) binding, reducing downstream G-protein signaling Inhibit neutrophil migration and recruitment to inflamed or tumorous tissues Reduce oxidative burst and granule release (notably via CXCR1 inhibition) Disrupt tumor-promoting inflammation and neutrophil-mediated support of tumors