CXCL5 is an ELR+CXC chemokine characterized by a Glu-Leu-Arg (ELR) motif preceding the characteristic CXC sequence. CXCL5 chemoattracts and activates neutrophils during inflammation through the binding to CXCR2. CXCL5 occurs in different NH2- and COOH-truncated forms, and both NH2-terminal and COOH-terminal truncation result in an increase in neutrophil chemotactic potency. CXCL5(8–78) and CXCL5(9–78) induce a higher neutrophil influx in vivo compared with CXCL5(1–78). CXCL5 regulates the availability of binding sites for other ELR+ CXC chemokines released during inflammation, through its interaction with erythrocyte duffy antigen receptor (DARC). As a result, CXCL5 induces the increase of CXCL1 and CXCL2 in a model of pulmonary inflammation. Therefore, CXCL5 acts as a regulator of chemokine scavenging and pulmonary host defense to bacterial infection. Lung epithelial cells express CXCR2; consequently, CXCL5 may modulate neutrophil transepithelial and transendothelial migration. Mouse CXCL5 is the ortholog of human CXCL6.