CXCR1

C-X-C chemokine receptor type 1 (CXCR1, IL-8RA, CD128a) is a Gαi-coupled seven-transmembrane receptor that, together with CXCR2, mediates neutrophil responses to ELR+ CXC chemokines. CXCR1 is distinguished by its restricted high-affinity ligand repertoire: it is activated by CXCL6 (GCP-2) and, uniquely, by the monomer form of CXCL8 (IL-8), whereas CXCR2 responds to a much broader set of ELR+ chemokines. Expressed on neutrophils, basophils, mast cells, monocytes and a subgroup of NK cells, CXCR1 triggers oxidative burst, granule enzyme release ( elastase, myeloperoxidase), integrin-mediated adhesion and chemotaxis upon ligand binding. CXCR1 functions as a rheostat of neutrophil activation in bacterial infection and acute inflammation, and its internalization/desensitization by excess IL-8 contributes to neutrophil paralysis in sepsis. In cancer, CXCR1 marks neutrophil myeloid-derived suppressor cells and breast cancer stem-like cells, and CXCR1 blockade with reparixin has been shown to target these populations in experimental settings.