Monocyte Chemoattractant Protein‐1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and Controversies

Abstract

Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2(-/-) and CCR2(-/-) mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease.

Treatment with bindarit, an inhibitor of MCP-1 synthesis, protects mice against trinitrobenzene sulfonic acid-induced colitis

“…MCP-1 is a prototypic inflammatory chemokine which targets monocytes, T lymphocytes, and other cells expressing the C-C chemokine receptor [42]. However, an array of inducible chemokines is produced under various inflammatory conditions, and all them co-operate with cytokines to further increase leukocyte recruitment to the site of inflammation [43].…”

Monocyte chemoattractant protein–1 −2518 A/G single nucleotide polymorphism in Chinese Han patients with ocular Behçet's disease

“…A typical example of a so-called CC type chemokine is monocyte chemotactic protein (MCP)-1 [13]. MCP-1 is a potent chemokine released by lymphocyte, monocytes, mast cells, and eosinophils during inflammation [14,15]. Ocular cells, such as the retinal pigment epithelial cell cultured in vitro, have also been shown to produce MCP-1 [16].…”

Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis

“…Furthermore, MCP-1 has been expressed in various types of tissues such as the thymus, spleen, kidney, liver, and lung [26]. MCP-1 has been shown to be expressed in many different inflammatory diseases, such as atherosclerosis, allergic asthma, idiopathic pulmonary fibrosis [27], and inflammatory bowel disease [28].…”