Chemokines are a family of small chemotactic cytokines, or proteins secreted by cells. Chemokines share the same structure similarities such as small size, and the presence of four cysteine residues in conserved locations in order to form their 3-dimensional shape. Some of the chemokines are considered pro-inflammatory which can be induced to recruit cells of the immune system to a site of infection during an immune response, while others are considered homeostatic and are implied in controlling the migration of cells during normal processes of tissue maintenance and development. There are four members of the chemokine family: C-C kemokines, C kemokines, CXC kemokines and CX3C kemokines. The C-C kemokines have two cysteines nearby the amino terminus. There have been at least 27 distinct members of this subgroup reported for mammals, called C-C chemokine ligands-1 to 28. Chemokine ligand 15 (CCL15/MIP-1δ), also known as leukotactin-1, MIP5, MIP1 and HCC-2, is a small cytokine belonging to the C-C chemokine family. CCL15/MIP-1δ is prevantly expressed in liver, small intestine, colon, and in certain leukocytes and macrophages of the lung. It is chemotactic for neutrophils, monocytes, and lymphocytes and elicits its effects by binding to cell surface chemokine receptors like CCR1 and CCR3.
Chemotactic factor that attracts T-cells and monocytes, but not neutrophils, eosinophils, or B-cells. Acts mainly via CC chemokine receptor CCR1. Also binds to CCR3. CCL15(22-92), CCL15(25-92) and CCL15(29-92) are more potent chemoattractants than the small-inducible cytokine A15.
CCL16/HCC-4, a chemokine poorly characterized at the functional level. Human CCL16/HCC-4 is a member of the CC family, and its gene maps to human chromosome 17q. In the mouse, only a pseudogene has been identified to date. CCL16/HCC-4 is a functional ligand for CCR1, CCR2, CCR5, and CCR8. Recombinant CCL16/HCC-4 demonstrated chemotactic activity on human monocytes and lymphocytes. Based on the ability of human chemokines to exert activity on and bind to murine receptors, the TSA mouse adenocarcinoma cell line was transfected with human CCL16/HCC-4 cDNA and, in comparison with other cytokines, was shown to be the faster inducer of systemic immune response due to massive, prompt infiltration of leukocytes.
CCL16 is a member of CC chemokine family. CCL16 cDNA encodes a 120 amino acid peptide along with a 23 amino acids signal peptide that is cleaved to generate 97 amino acid protein. CCL16 is distantly related to other CC chemokines, showing less than 30% sequence identity. CCL16 elicits its effects on cells by interacting with cell surface chemokine receptors such as CCR1, CCR2, CCR5 and CCR8. Recombinant CCL16 has been shown to chemoattract human monocytes and THP1 cells but not resting lymphocytes nor neutrophils. CCL16 has potent myelosuppressive activity, suppresses proliferation of myeloid progenitor cells. CCL16ninduces a calcium flux in THP1 cells that can be desensitized by prior exposure to RANTES, suggesting that CCL16 and RANTES share the same receptor in THP1 cells.
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