Recombinant Human CCL5/RANTES Protein

CCL5, also known as RANTES (Regulated upon Activation, Normal T cell Expressed and presumably Secreted), is an 8 kDa beta-chemokine that plays a primary role in the inflammatory immune response by means of its ability to attract and activate leukocytes (1-3). Human and mouse RANTES exhibit cross-species activity on human and mouse cells (4). Mature human CCL5 shares 75%-84% aa seqeuence identity with canine, cotton rat, feline, mouse, and rat CCL5 (5). CCL5 is secreted by many cell types at inflammatory sites, and it exerts a wide range of activities through the receptors CCR1, CCR3, CCR4, and CCR5 (6, 7). Inflammatory responses can be impaired by the sequestration of CCL5 by the cytomegalovirus protein US28 (8). In humans, CCR5 binding to CCL5 inhibits the infectivity of R5 (M-tropic) but not X4 (T-tropic) strains of HIV-1 (9). The two N-terminal residues of CCL5 can be removed by CD26/DPPIV, generating a protein that functions as a chemotaxis inhibitor and more effectively blocks M-tropic HIV-1 infection of monocytes (10). Oligomerization of CCL5 on glycosaminoglycans is required for CCR1-mediated leukocyte adhesion and activation as well as CCL5’s interaction with the chemokine CXCL4/PF4 (11-13). The deposition of CCL5 on activated vascular endothelial cells is crucial for monocyte adhesion to damaged vasculature, but CCL5 oligomerization is not required for the extravasation of adherent leukocytes (14-16). CCL5 is upregulated in breast cancer and promotes tumor progression through the attraction of proinflammatory macrophages in addition to its actions on tumor cells, stromal cells, and the vasculature (17).