Ccl8

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

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

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

CCL8 (CC-chemokine ligand 8) or MCP-2, is a small cytokine of the CC-chemokine family. In humans, the chemokine is encoded by the CCL8 gene on chromosome 17q11.2, which is located in the vicinity of a larger cluster of other chemokine gene loci. CCL8 binds to the chemokine receptors CCR1, CCR2B and CCR5.

CCL8 is involved to a large extent in inflammatory processes. It is chemotactic for numerous immune cells, such as mast cells, eosinophil and basophil granulocytes, monocytes, T cells and NK cells. Apparently CCL8 and its receptor CCR8 play an important role in atopic dermatitis. It is able to attract inflammatory highly specific T-helper cells of type Th2. These in turn are able to produce interleukin-5 , which increases eosinophilic inflammation (Islam SA et al. 2011).

In animal experiments, CCL8 expression in serum correlates with the survival rate of bone marrow transplants and, together with other cytokines, also serves as a biomarker for a GVHD reaction in humans.

Due to its binding to the CCR5 chemokine receptor, a high-affinity transmembrane receptor for HIV1, CCL8 inhibits the infection of cells with the HIV1 virus.

For the invasiveness of a malignant tumor (studies on malignant melanoma and breast carcinoma) the gradient of the CCL8 concentration in a tumor tissue seems to play a role (see also CCL12).

1. Barbai T et al(2015) The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma. Oncotarget 6:29111-19128.
2. Berger M et al (2013) Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients. Bone Marrow Transplant 48:1230-1236.
3. Farmaki E et al (2016) A CCL8 gradient drives breast cancer cell dissemination. Oncogene 35:6309-6318.
4. Islam SA et al (2011) Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ T(H)2cells
   .Nat Immunol 12:167-77
5. Yamamoto M et al (2011) Early expression of plasma CCL8 closely correlates with survival rate of acute graft-vs. host disease in mice. Exp Hematol 39:1101-1112.