Recombinant Human CCL2/MCP-1

CCL2, also called monocyte chemotactic protein-1 (MCP-1) or JE, is a member of the C-C or beta chemokine family that is best known as a chemotactic agent for mononuclear cells ^{[1, 2]}. Human CCL2 cDNA encodes a 99 amino acid (aa) precursor protein with a 23 aa signal peptide and a 76 aa mature protein ^[2]. Removal of the first 5 aa of the mature protein, including the N-terminal pyrrolidone carboxylic acid-modified glutamine, occurs naturally by metalloproteinase cleavage and down-regulates activity but not receptor binding ^[3]. CCL2 may form multiple bands from 8.7-13.5 kDa on SDS-PAGE due to non-covalent dimerization and variable carbohydrate content^[3]. Mature human CCL2 shares 78-79% aa identity with canine, porcine and equine CCL2, while mouse and rat express a form of CCL2 that is extended by 49 aa and shares only ~56% aa identity within the common region. Human CCL2 can, however, induce a response in murine cells ^[4]. Fibroblasts, glioma cells, smooth muscle cells, endothelial cells, lymphocytes and mononuclear phagocytes can produce CCL2 either constitutively or upon mitogenic stimulation, but monocytes and macrophages appear to be the major source ^{[1, 2]}. In addition to its chemotactic activity, CCL2 induces enzyme and cytokine release by monocytes, NK cells and lymphocytes, and histamine release bybasophils that express its receptor, CCR2 ^[2]. Additionally, it promotes Th2 polarization in CD4+ T cells ^[5]. CCL2-mediated recruitment of monocytes to sites of inflammation is proposed to play a role in the pathology of atherosclerosis, multiple sclerosis and allergic asthma ^{[6, 7]}.

Reference

[1]. Yoshimura, T. et al. (1989) FEBS Lett. 244:487.

[2]. Deshmane, S.L. et al. (2009) J. Interferon Cytokine Res. 29:313.

[3]. Proost, P. et al.(1998) J. Immunol. 160:4034.

[4]. Ju Lee, H. et al. (2015) J. Immunol. 194:3634.

[5]. Luther, S.A. and J.G. Cyster (2001) Nat. Immunol. 2:102.

[6]. Daly, C. et al. (2003) Microcirculation 10:247.

[7]. Aukrust, P. et al. (2008) Arterioscler. Thromb. Vasc. Biol. 28:1909