Recombinant Mouse CCL5

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 mouse CCL5 shares 100% aa sequence identity with rat CCL5 and 75% - 88% with canine, cotton rat, feline, and human 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].

Reference

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[8] Randolph-Habecker, J.R. et al. (2002) Cytokine 19:37.

[9] DeVico, A.L. and Gallo, R.C. (2004) Nat. Rev. Microbiol. 2:401.

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[11] Appay, V. et al. (1999) J. Biol. Chem. 274:27505.

[12] Proudfoot, A.E.I. et al. (2003) Proc. Natl. Acad. Sci. 100:1885.

[13] von Hundelshausen, P. et al. (2005) Blood 105:924.

[14] von Hundelshausen, P. et al. (2001) Circulation 103:1772.

[15] Zernecke, A. et al. (2008) Arterioscler. Thromb. Vasc. Biol. 28:1897.

[16] Baltus, T. et al. (2003) Blood 102:1985.

[17] Soria, G. and A. Ben-Baruch (2008) Cancer Lett. 267:271