Recombinant Mouse CXCL3/DCIP-1 Protein

CXCL3 is also known as MIP-2 beta (macrophage inflammatory protein 2 beta), or DCIP-1 (dendritic cell inflammatory protein-1) in mouse, CINC2 (cytokine-induced neutrophil attractant 2) in rat, and GRO-gamma (growth-regulated oncogene gamma) in humans (1, 2). It is an 8 kDa proinflammatory member of the CXC subfamily of heparin-binding chemokines, also called alpha chemokines (1 - 4). The Glu-Leu-Arg (ELR) motif near the CXCL3 N-terminus confers angiogenic properties and distinguishes it from interferon-inducible ELR^- CXC chemokines, which are angiostatic (4). ELR⁺ and ELR^- chemokines use CXCR2 and CXCR3 receptors, respectively (3, 4). Mature mouse CXCL3 shares 88% and 57% amino acid (aa) sequence identity with rat and human CXCL3, respectively. Among mouse ELR⁺ chemokines, it shares 82% aa sequence identity with CXCL2/GRO-beta /MIP-2 and 34% - 58% with CXCL1/GRO-alpha /KC, CXCL5/ENA-78 and CXCL7/NAP-2. Due to their similar sequence and activity, CXCL2 and CXCL3 are sometimes referred to collectively as CXCL2/3, but are separate gene products (4 - 6). Mouse CXCL3 expression is induced in macrophages and early in maturation of DC by bacterial products such as lipopolysaccharides, and other inflammatory mediators (1, 7). It is chemotactic for CXCR2-expressing neutrophils, helping to recruit them to areas of inflammation (1, 7). ELR⁺ chemokines also elicit endothelial cell chemotaxis, stimulating angiogenesis and playing a role in tumor development (3, 4). ELR⁺ chemokines upregulated by ischemia play a role in ischemia-reperfusion injury (5, 6). A decoy receptor, DARC (Duffy antigen receptor for chemokines) competes with CXCR2 for ELR⁺ chemokine binding, thus downregulating their effect (8). Neutrophil influx may also be downregulated by MMP-12, which has been found to inactivate CXCL3 and other ELR⁺ chemokines by cleaving them at the ELR site (9).