Chemokines

Small peptides of 8-11 kDa. Subfamily of cytokines (about 50 are currently known in humans) with strong chemotactic activity in response to inflammatory signals (e.g. lipopolysaccharides). They thus act mainly locally. Chemokines mediate their effects through interaction with specific chemokine receptors expressed on a variety of cell types (T cells, NK cells, monocytes, macrophages, eosinophil and basophil granulocytes and dendritic cells) and transmit their signals via so-called G proteins. Increased chemokine expressions are found in chronic inflammatory diseases such as HIV infection, atopic eczema, bronchial asthma, allergic rhinitis and psoriasis vulgaris. Chemokines play a positive role e.g. in wound healing, haematopoiesis (blood formation) or the defence against infections. The fact that chemokine receptors are present not only on inflammatory cells but also on tumor cells and endothelial cells suggests that they are also involved in the migration of tumor cells or the metastatic behavior of the various tumors.

The following subfamilies have been classified:

• CC chemokines (or β chemokines): They contain two directly adjacent amino-terminal cysteine residues.
• CXC chemokines (or α chemokines): They contain C1 and C2 separated by a single amino acid.
• CX3C chemokines: Contain C1 and C2 separated by three amino acids.
• C-chemokines: Contain only the first and third cysteine residues (C1 and C3).
• The fifth family of chemokines is encoded by viral genes.

Almost all chemokines contain four conserved cysteine amino acid residues (C1-C4). The nomenclature for chemokines is not yet uniform. One part is named according to its specific function (e.g. MCP-1 = monocyte chemotactic protein 1), another according to its cellular source (e.g. RANTES = regulated upon activation, normal T-expressed and secreted) or arbitrarily like interleukin-8.

One member of the CC chemokine family, CCL13, regulates the migration of monocytes, macrophages, T cells and eosinophilic granulocytes via their CCR2 and CCR3 chemokine receptors. CCL13 is increasingly expressed in the skin of patients with systemic scleroderma. The serum level of this chemokine (diagnostic marker) is also elevated.