Ccl9

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 (see figure), 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.

CCL9 (CC-chemokine ligand 9), also known as Macrophage Inflammatory Protein 1, MIP-1, Macrophage inflammatory protein-related protein-2, MRP-2 or CCF18 is a small cytokine of the CC chemokine family.

CCL9 is formed and secreted by follicle-associated epithelia (FAE) found around Peyer's plaques. CCL9 acts as an attractor for dendritic cells expressing the antigen CD11b and the chemokine receptor CCR1 on their surface.

CCL9 binds to osteoclasts via its chemokine receptor CCR1. Osteoclasts are influenced by CCL9 in their polarisation and motility. The CCR1 receptor protein is the chemokine receptor most frequently found on the surface of osteoclasts. The chemokine plays an important role in the resorption of bone. CCL9 is also expressed by macrophages and myeloid cells.

CCL9 is involved in inflammatory processes. It is formed by the "lymph follicle-associated tissue" located in the intestine around Peyer's plaques. CCL9 binds to dendritic cells via CCR1 and the integrin alpha M (= CD11b).

The murine CCL9 was identified as murine CCL10. It is largely homologous to the human CCL15.

1. Lean JM et al (2002) CCL9/MIP-1gamma and its receptor CCR1 are the major chemokine ligand/receptor species expressed by osteoclasts. J Cell Biochem 87:386-393.
2. Nakato G et al (2015) Distinct microRNA expression profiles in follicle-associated epithelium and villous epithelium. Genome Data 5:388-390.
3. Swamydas M et al (2013) Mesenchymal stem cell-derived CCL-9 and CCL-5 promote mammary tumor cell invasion and the activation of matrix metalloproteinases. Cell Adh Migr 7:315-324.
4. Yang M et al (2006) Chemokines and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro. Blood 107:2261-2270.
5. Zhao X et al (2003) CCL9 is secreted by the follicle-associated epithelium and recruits dome region Peyer's patch CD11b+ dendritic cells. J Immunol 171:2797-2803.