Monocyte chemoattractant protein-1 (MCP-1): an overview

Abstract

Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

FIG. 1.

Schematic representation of the three-dimensional structure of chemokines. Three-dimensional representation of a chemokine, where α and β sheet, as well as the cysteine residues and the 30s and 40s loops, are shown. Note that all chemokines share a typical Greek key structure that is stabilized by disulfide bonds between conserved cysteine residues. The term Greek key refers to a kind of secondary structure or motif of a protein sequence.

FIG. 2.

Amino-acid sequence alignment of human MCPs. Conserved cysteine residues are indicated by alignment and spacing. Consensus sequence residues are in dark grey, whereas conserved and mutated CCL2 residues are shown in black and light grey, respectively.

FIG. 3.

Schematic representation of CCL2 structure. Note that all the domains are also indicated.