Chemokine (C-C motif) ligand 9 (CCL9) is a small

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

belonging to the CC

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In additio ...

family. It is also called ''macrophage inflammatory protein-1 gamma'' (MIP-1γ), ''macrophage inflammatory protein-related protein-2'' (MRP-2) and CCF18, that has been described in rodents. CCL9 has also been previously designated CCL10, although this name is no longer in use. It is secreted by follicle-associated epithelium (FAE) such as that found around

Peyer's patch Peyer's patches (or aggregated lymphoid nodules) are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. * Reprinted as: * Peyer referred to Peyer's patches as ''plexus'' or ''agmina glandularum'' (c ...

es, and attracts dendritic cells that possess the cell surface molecule

CD11b Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as ''macrophage-1 antigen'' (Mac-1) or '' complement receptor 3'' (CR3). ITGAM is also known as CR3A, and cluster of dif ...

and the

chemokine receptor Chemokine receptors are cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. There have been 20 distinct chemokine receptors discovered in humans. Each has a rhodopsin-like 7-trans ...

CCR1 C-C chemokine receptor type 1 is a protein that in humans is encoded by the ''CCR1'' gene. CCR1 has also recently been designated CD191 (cluster of differentiation 191). Function This gene encodes a member of the beta chemokine receptor fami ...

. CCL9 can activate

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

s through its receptor CCR1 (the most abundant chemokine receptor found on osteoclasts) suggesting an important role for CCL9 in

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

. CCL9 is constitutively expressed in macrophages and myeloid cells. The

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

for CCL9 is located on

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

11 in mice. CCL9 is a chemokine involved in the process of signaling an antileukemic response and is a potential form of immunotherapy for chronic myelogenous leukemia (CML). CML is a type of cancer in which the bone marrow produces too many red blood cells. This is caused by

chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translo ...

, a mutation in which the abnormal gene BCR-ABL, is turned into a CML cell. CML starts off as a myeloproliferative for example in

sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...

or extreme

granulocytosis In medicine, granulocytosis is the presence of an increased number of granulocytes in the peripheral blood. Often, the word refers to an increased neutrophil granulocyte count (neutrophilia), but granulocytosis formally refers to the combination of ...

but if left untreated, it could transform into an acute form of leukemia. In order to treat CML, alpha and beta interferons (INFs) are used to regulate the process of binding the protein ICSBP to the gene BCR-ABL. CCL9 was proved to be a gene induced by ICSBP and IFN alpha and also a requirement in the expression of ICSBP in BCR-ABL transformed cells to generate an anti-leukemic immune protection via experimentation. CCL6 and CCL9 were overexpressed in BaF3 cells and injected with BCR-ABL into syngeneic mice. Although the mice still developed leukemia, it delayed the advancement of the disease by several weeks proving that CCL6 and CCL9 contribute to the creation of an anti-leukemic response within infected cells.

References

Cytokines {{protein-stub