Novel approach to inhibiting chemokine function

CC chemokine ligand 2 (CCL2) or monocyte chemoattractant protein-1 (MCP-1) is an important chemoattractant for monocytes and macrophages (Deshmane et al, 2009). CCL2 is the main ligand for the chemokine receptor CCR2, which mediates CCL2’s biological activity. CCR2 is a seven transmembrane spanning Gai protein-coupled receptor (GPCR) constitutively expressed at high levels on monocytes and macrophages. CCL2 expression is induced in a variety of tissue resident cells (e.g. endothelial cells) and immune cells (e.g. macrophages) by inflammatory mediators (e.g. TNF, LPS and IFNg). CCL2 mobilizes monocytes out of the bone marrow and recruits circulating monocytes into sites of infection and inflammation. Perhaps more than any other chemokine system, CCL2 and CCR2 have been shown to play important pathological roles in vivo in murine models of disease. For example, in murine models of atherosclerosis, experimental autoimmune encephalomyelitis and obesity-induced diabetes, mice deficient in CCL2 and/or CCR2 have markedly reduced monocyte accumulation in diseased tissue and are protected from disease (Charo & Ransohoff, 2006). Murine studies have also demonstrated