Recombinant Mouse CCL9/10/MIP-1 gamma Protein

Mouse CCL9/10 (also named MIP-1 gamma and MRP-2) is an 11 kDa, secreted, monomeric polypeptide that belongs to the beta (or CC) intercrine family of chemokines (1 - 3). Based on its activity and amino acid (aa) sequence, it is further classified as a member of the NC6 or six cysteine-containing CC subfamily of chemokines (2, 4, 5). This subfamily contains four N-terminally extended chemokines, two human (CCL15 and CCL23) and two mouse (CCL9 and CCL10). Within this subfamily, there are no human-to-rodent interspecies orthologs. Mouse CCL9/10 is synthesized as a 122 aa precursor that contains a 21 aa signal sequence and a 101 aa mature region with six cysteines. As noted, the mature region has an expanded N-terminus relative to other CC family members, and it forms a third intrachain disulfide bond with its two extra cysteines (3 - 7). Mouse CCL9/10 is 75% aa identical to rat CCL9/10 (8). Chemokines are known to undergo proteolytic processing to generate multiple isoforms. NC6 chemokines are usually only marginally active at full length, but are converted to highly active forms upon N-terminal truncation. Mature CCL9, in the presence of inflammatory fluids, is naturally truncated by 28, 29 or 30 aa at the N-terminus, generating a highly active, 8 kDa, 71 - 73 aa CCR1 ligand. In contrast, other CCR1 ligands, CCL3/MIP-1 alpha and CCL5/RANTES, lose their potency when proteolytically processed. CCL9/10 is constitutively secreted, and circulates as a full-length molecule. Any onset of inflammation with subsequent enzyme release may act on local NC6 chemokines, generating early, potent leukocyte chemoattractants (5, 7).