In molecular biology, CD18 (Integrin beta chain-2) is an integrin beta chain protein that is encoded by the ITGB2 gene in humans. Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses. CD18 also exists in soluble, ligand binding forms. Genetically-inherited deficiencies in the ITGB2 gene can lead to reduced surface expression of the CD18 protein, leading to the immunodeficiency leukocyte adhesion deficiency.
Structure and function The ITGB2 protein product is CD18. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain, and are crucial for cells to be able to efficiently bind to the extracellular matrix. This is especially important for neutrophils, as cellular adhesion plays a large role in extravasation from the blood vessels. A given chain may combine with multiple partners resulting in different integrins. The known binding partners of CD18 are CD11a, CD11b, CD11c and CD11d. Binding of CD18 and CD11a results in the formation of lymphocyte function-associated antigen-1 (LFA-1), a protein found on B cells, all T cells, monocytes, neutrophils and NK cells. LFA-1 is involved in adhesion and binding to antigen presenting cells through interactions with the surface protein ICAM-1. Binding of CD18 and CD11b-d results in the formation of complement receptors (e.g. Macrophage-1 antigen receptor, Mac-1, when bound to CD11b), which are proteins found largely on neutrophils, macrophages and NK cells. These complement receptors participate in the innate immune response by recognizing foreign antigen peptides and phagocytizing them, thus destroying the antigen.
Clinical significance In humans, lack of functional CD18 causes leukocyte adhesion deficiency, a disease defined by a lack of leukocyte extravasation from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue. This subsequently reduces the ability of the individual's immune system to fight off infection, making them more susceptible to foreign infection than those with functional CD18 proteins. The beta 2 integrins have also been found in a soluble form, meaning they are not anchored into the plasma membrane of the cell, but rather exist outside of the cell in the plasma, and are capable of ligand binding. The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.
Interactions CD18 has been shown to interact with:
See also leukocyte adhesion deficiency integrin
References
Further reading
External links CD18+antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH) ITGB2 Info with links in the Cell Migration Gateway Archived 11 December 2014 at the Wayback Machine Human ITGB2 genome location and ITGB2 gene details page in the UCSC Genome Browser.
