In molecular biology,CD18 (Integrin beta chain-2) is anintegrin beta chainprotein that is encoded by theITGB2gene in humans.[5] Upon binding with one of a number of alpha chains, CD18 is capable of forming multipleheterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses.[5][6] CD18 also exists in soluble, ligand binding forms. Genetically-inherited deficiencies in theITGB2 gene can lead to reduced surface expression of the CD18 protein, leading to the immunodeficiencyleukocyte adhesion deficiency.
TheITGB2 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 theextracellular matrix.[5] 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.
Binding of CD18 and CD11b-d results in the formation ofcomplement receptors (e.g.Macrophage-1 antigen receptor, Mac-1, when bound to CD11b),[8] which are proteins found largely on neutrophils, macrophages and NK cells. These complement receptors participate in theinnate immune response by recognizing foreign antigen peptides andphagocytizing them, thus destroying the antigen.
In humans, lack of functional CD18 causesleukocyte adhesion deficiency, a disease defined by a lack of leukocyteextravasation from blood into tissues, which is the inability of circulating leukocytes to respond to foreign bodies present in the tissue.[10] 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 asoluble 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.[11] The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.[12]
^Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA (July 1987). "Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency".Cell.50 (2):193–202.doi:10.1016/0092-8674(87)90215-7.PMID3594570.S2CID40388710.
Schymeinsky J, Mócsai A, Walzog B (August 2007). "Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications".Thrombosis and Haemostasis.98 (2):262–73.doi:10.1160/th07-02-0156.PMID17721605.S2CID41094726.
