Recombinant Human CXCL5/ENA-78 Protein

CXCL5, also known as epithelial cell-derived neutrophil-activating peptide (ENA-78), is an 8 kDa proinflammatory member of the CXC subfamily of chemokines. Its Glu-Leu-Arg (ELR) motif confers angiogenic properties and distinguishes it from ELR-CXC chemokines which are angiostatic (1-3). Human CXCL5 shares 57% amino acid (aa) sequence identity with mouse and rat CXCL5. Among other human ELR⁺ chemokines, it shares 77% aa sequence identity with CXCL6/GCP-2 and 35%-51% with CXCL1/GRO alpha, CXCL2/GRO beta, CXCL3/GRO gamma, CXCL7/NAP-2, and CXCL8/IL-8. Inflammatory stimulation up-regulates CXCL5 production in multiple hematopoietic cell types, fibroblasts, endothelial cells, and vascular smooth muscle cells. In vivo, CXCL5 is elevated at sites of inflammation and pulmonary fibrosis where it promotes neutrophil infiltration and activation as well as angiogenesis (3-6). Its up-regulation contributes to increased vascularization, tumor growth, and metastasis in many cancers (6-9). Full length CXCL5 (78 aa) is trimmed at the N-terminus by cathepsin G and chymotrypsin to ENA-74 (74 aa) and ENA-70 (70 aa), with the shortened forms showing increased potency relative to full length CXCL5 (10, 11). CXCL5 exerts its effects primarily through interactions with CXCR2 (6, 12). It also binds duffy antigen receptor for chemokines (DARC), which can limit CXCR2-mediated responses (13, 14).