MOLECULES OF THE IMMUNE SYSTEM
Homeostatic and Inflammatory Chemokines
As opposed to classic leukocyte chemoattractants, which have little specificity, chemokines induce the recruitment of well-defined cell types and leukocyte subsets. For example, CXC-chemokines can attract neutrophils but not macrophages, while CC-chemokines preferentially induce the migration of macrophages. To date, about 40 chemokines have been identified in humans. They mainly act on neutrophils, monocytes/macrophages, lymphocytes, and eosinophils and play an essential role in host defense mechanisms. In addition, chemokines regulate the lymphoid organ development, the functioning of the nervous system, and may stimulate tumor cell metastasis.
Chemokines have been structurally classified into four main subfamilies: (1) C, (2) CC, (3) CXC and (4) ÑX3C depending on the location of cysteine (C) between other amino acids (X) in the chemokine's protein molecule sequence. Addition of the letter L refers to chemokines themselves and means Ligand whereas the letter R is related to chemokine receptors and denotes Receptor. For example, CCR7 is the receptor for CCL19 (Exodus-3, ELC) and CCL21 (Exodus-2, SLC) important for cell migration to the secondary lymphoid organs. Typically, chemokine receptors are linked with G proteins.
There are two functional groups of chemokines.
Homeostatic chemokines are produced in certain tissues and cells, and are responsible for homing leukocytes in particular organs or tissues. Tissue-specific chemokine receptors are closely associated to various cell adhesion molecules to provide settling organs of the immune system with lymphocytes and other cell types. As compared to inflammatory chemokines, the homeostatic chemokines exert a more diverse range of functions. They may be involved in the organogenesis, migration of progenitor cells, and cell development. However, homeostatic chemokines can also be involved in the carcinogenesis and metastasis of cancer cells. The samples of homeostatic cytokines are CCL27 (cutaneous T-cell-attracting chemokine, CTACK), CCL28 (mucosae-associated epithelial chemokine, MEC), etc.
Inflammatory chemokines are constituted under pathological conditions due to pro-inflammatory stimuli from sites of infection, injury, or tissue damage and take an active part in the inflammatory response attracting a wide variety of cells in both the innate and adaptive immunity. Under the influence of inflammatory chemokines, cells will extravasate from the blood vessel and follow the gradient to pro-inflammatory stimuli. This group of chemokines is also recruited in wound healing. The samples of inflammatory chemokines are CCL2 (MCP-1), CCL8 (MCP-2), CCL11 (Eotaxin-1), CXCL8 (IL-8), etc.