CCL2

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, in some virus species and bacteria. In humans, about 50 chemokines are currently known.

A highly conserved structural feature of all chemokines is a fixed group of cysteine residues stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for their fixed 3-dimensional structure.

In CC chemokines the cysteines follow each other directly (see figure), in CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a variety of immune cells. They mediate their signals by binding to chemokine receptors via G-proteins. Some chemokines have proinflammatory effects, while others have regulatory effects in tissue formation and homeostasis.

CCL2, also called CC-chemokine ligand 2 or "monocyte chemoattractant protein-1" or, MCP-1, is a cytokine of the CC-chemokine family. In humans, the CCL2 gene is located on chromosome 17. CCL2 is a ligand of the receptors CCR2 and CCR4 (see below CCR2 gene).

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, in some virus species and bacteria. In humans, about 50 chemokines are currently known.

A highly conserved structural feature of all chemokines is a fixed group of cysteine residues stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for their fixed 3-dimensional structure.

In CC chemokines the cysteines follow each other directly (see figure), in CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a variety of immune cells. They mediate their signals by binding to chemokine receptors via G-proteins. Some chemokines have a proinflammatory effect, others have a regulatory effect in the formation and homeostasis of tissues.

CCL2 is produced at sites of inflammation by monocytes, memory T cells and dendritic cells. It binds to proteoglycans of endothelial cells via its CCR2 receptor.

CCL2 has a chemotactic effect on monocytes and basophilic granulocytes, but not on eosinophilic granulocytes. In basophilic granulocytes and mast cells, CCL2 induces degranulation. CCL2 enhances a tumor "fighting" activity of monocytes. However, the CCL2-CCR2 complex also appears to cause direct growth acceleration of tumor cells under certain circumstances.

CCL2 is also produced by neurons, astrocytes and microglia. The CCL2-CCR2 complex is involved in a number of neurodegenerative and neuroimmunological diseases such as Alzheimer's dementia (G30.9), ischemic brain insults and multiple sclerosis (G35.-). In glial cells of Alzheimer patients there is an increased CCL2 expression.

CCL2 together with CCL5 (RANTES) plays a role in osteoclast differentiation.

CCL2 is also thought to be involved in the pathogenesis of chronic inflammatory diseases such as psoriasis, rosacea, rheumatoid arthritis (M06.99) and others.

High levels of CCL2/CCR2 could also be detected in HIV-infected patients during the retroviral therapy phase. Direct influences of CCL2 on HIV replication are suspected. The CCL2/CCR2 axis also plays an important pathogenetic role in the inflammatory responses of COVID-19 infection.

CCL2, CCL3, CCL5, CXCL4, CXCL10 and CXCL16 induce fibrosis in autoimmune hepatitis (K75.4) by activating and attracting hepatic stellate cells. CCL2 seems to play a prominent role in this process and may be a therapeutic target in inflammatory diseases.

1. Ansari AW et al (2014) Immuno-pathomechanism of liver fibrosis: targeting chemokine CCL2-mediated HIV:HCV nexus. J Transl Med 12:341...
2. Bose S et al (2013) Role of chemokine CCL2 and its receptor CCR2 in neurodegenerative diseases. Arch Pharm Res 36:1039-1050.
3. Czaja AJ (2014) Review article: chemokines as orchestrators of autoimmune hepatitis and potential therapeutic targets. Aliment Pharmacol Ther 40:261-279.
4. Covino DA et al.(2016) The CCL2/CCR2 Axis in the Pathogenesis of HIV-1 Infection: A New Cellular Target for Therapy? curr drug targets 17:76-110.
5. Lim SY et al (2016) Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget 7:28697-28710.
6. O'Connor T et al. (2015) CCL2-CCR2 Signaling in Disease Pathogenesis. Endocr Metab Immune Disord Drug Targets 15:105-118.
7. Palomino DC et al (2015) Chemokines and immunity. Einstein (Sao Paulo) 13:469-473 .
8. Steinhoff M et al (2013) New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol 69(6 Suppl 1):S15-26 .