View source for Integrin beta 2

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox gene}}
In molecular biology, '''CD18''' ('''Integrin beta chain-2''') is an [[integrin]] beta chain [[protein]] that is encoded by the ''[[ITGB2]]'' [[gene]] in humans.<ref name= AAM1990>{{cite journal|last1=Amin Aanout|first1=M.|title=Structure and Function of the Leukocyte Adhesion Molecules CD11/CD18|journal=Blood|date=March 1, 1990|volume=75|issue=5|pages=1037–1050|doi=10.1182/blood.V75.5.1037.1037|pmid=1968349|doi-access=free}}</ref> 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.<ref name= AAM1990 /><ref>{{cite web|title=ITGB2 integrin subunit beta 2 [ Homo sapiens (human) ]|url=https://www.ncbi.nlm.nih.gov/gene/3689}}</ref> 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]].<ref name= AAM1990 /> 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]],<ref name= LFA-1>{{cite journal | vauthors = Verma NK, Kelleher D | title = Not Just an Adhesion Molecule: LFA-1 Contact Tunes the T Lymphocyte Program | journal = Journal of Immunology | volume = 199 | issue = 4 | pages = 1213–1221 | date = August 2017 | pmid = 28784685 | doi = 10.4049/jimmunol.1700495 | doi-access = free }}</ref> [[CD11b]],<ref name= Mac-1>{{cite journal|last1=Todd|first1=R|title=The continuing saga of complement receptor type 3 (CR3)|journal=Journal of Clinical Investigation|date=1996|volume=98|issue=1|pages=1–2|doi=10.1172/jci118752|pmid=8690779|pmc=507390}}</ref> [[CD11c]] and [[CD11d]].<ref name= AAM1990 /> Binding of CD18 and CD11a results in the formation of lymphocyte function-associated antigen-1 ([[LFA-1]]),<ref name= LFA-1 /> a protein found on [[B cells]], all [[T cells]], [[monocytes]], [[neutrophils]] and [[NK cells]].<ref>{{cite journal|vauthors=Fekadu J, Modlich U, Bader P, Bakhtiar S|journal=International Journal of Molecular Sciences|title=Understanding the Role of LFA-1 in Leukocyte Adhesion Deficiency Type I (LAD I): Moving towards Inflammation?|year=2022|volume=23|issue=7|page=3578 |id=3578|doi=10.3390/ijms23073578|doi-access=free|pmid=35408940|pmc=8998723}}</ref>  LFA-1 is involved in adhesion and binding to [[antigen presenting cells]] through interactions with the surface protein [[ICAM-1]].<ref name=LFA-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),<ref name= Mac-1 /> 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 [[Phagocytosis|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.<ref>{{cite journal | vauthors = Kishimoto TK, Hollander N, Roberts TM, Anderson DC, Springer TA | title = Heterogeneous mutations in the beta subunit common to the LFA-1, Mac-1, and p150,95 glycoproteins cause leukocyte adhesion deficiency | journal = Cell | volume = 50 | issue = 2 | pages = 193–202 | date = July 1987 | pmid = 3594570 | doi=10.1016/0092-8674(87)90215-7| s2cid = 40388710 }}</ref> 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.<ref>{{cite journal | vauthors = Gjelstrup LC, Boesen T, Kragstrup TW, Jørgensen A, Klein NJ, Thiel S, Deleuran BW, Vorup-Jensen T | title = Shedding of large functionally active CD11/CD18 Integrin complexes from leukocyte membranes during synovial inflammation distinguishes three types of arthritis through differential epitope exposure | journal = Journal of Immunology | volume = 185 | issue = 7 | pages = 4154–68 | date = October 2010 | pmid = 20826754 | doi = 10.4049/jimmunol.1000952 | doi-access = free }}</ref> The soluble beta 2 integrins are ligand binding and plasma levels are inversely associated with disease activity in the autoimmune disease spondyloarthritis.<ref>{{cite journal | vauthors = Kragstrup TW, Jalilian B, Hvid M, Kjærgaard A, Østgård R, Schiøttz-Christensen B, Jurik AG, Robinson WH, Vorup-Jensen T, Deleuran B | title = Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis | journal = Arthritis Research & Therapy | volume = 16 | issue = 1 | pages = R42 | date = February 2014 | pmid = 24490631 | doi = 10.1186/ar4471 | pmc = 3978678 | doi-access = free }}</ref>

== Interactions ==
CD18 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[FHL2]],<ref name = pmid10906324>{{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = The Journal of Biological Chemistry | volume = 275 | issue = 43 | pages = 33669–78 | date = October 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 | doi-access = free }}</ref> 
* [[GNB2L1]],<ref name = pmid9442085>{{cite journal | vauthors = Liliental J, Chang DD | title = Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit | journal = The Journal of Biological Chemistry | volume = 273 | issue = 4 | pages = 2379–83 | date = January 1998 | pmid = 9442085 | doi = 10.1074/jbc.273.4.2379 | doi-access = free }}</ref>
* [[ICAM-1]],<ref name = pmid10352278>{{cite journal | vauthors = Kotovuori A, Pessa-Morikawa T, Kotovuori P, Nortamo P, Gahmberg CG | title = ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity | journal = Journal of Immunology | volume = 162 | issue = 11 | pages = 6613–20 | date = June 1999 | doi = 10.4049/jimmunol.162.11.6613 | pmid = 10352278 | s2cid = 40796900 | doi-access = free }}</ref><ref name = pmid11279101>{{cite journal | vauthors = Lu C, Takagi J, Springer TA | title = Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state | journal = The Journal of Biological Chemistry | volume = 276 | issue = 18 | pages = 14642–8 | date = May 2001 | pmid = 11279101 | doi = 10.1074/jbc.M100600200 | doi-access = free }}</ref><ref name = pmid7642561>{{cite journal | vauthors = Huang C, Springer TA | title = A binding interface on the I domain of lymphocyte function-associated antigen-1 (LFA-1) required for specific interaction with intercellular adhesion molecule 1 (ICAM-1) | journal = The Journal of Biological Chemistry | volume = 270 | issue = 32 | pages = 19008–16 | date = August 1995 | pmid = 7642561 | doi = 10.1074/jbc.270.32.19008 | doi-access = free }}</ref>  and
* [[PSCD1]].<ref name = pmid9765275>{{cite journal | vauthors = Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B | title = The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins | journal = The Journal of Biological Chemistry | volume = 273 | issue = 42 | pages = 27459–66 | date = October 1998 | pmid = 9765275 | doi = 10.1074/jbc.273.42.27459 | doi-access = free }}</ref><ref name = pmid10835351>{{cite journal | vauthors = Geiger C, Nagel W, Boehm T, van Kooyk Y, Figdor CG, Kremmer E, Hogg N, Zeitlmann L, Dierks H, Weber KS, Kolanus W | title = Cytohesin-1 regulates beta-2 integrin-mediated adhesion through both ARF-GEF function and interaction with LFA-1 | journal = The EMBO Journal | volume = 19 | issue = 11 | pages = 2525–36 | date = June 2000 | pmid = 10835351 | pmc = 212768 | doi = 10.1093/emboj/19.11.2525 }}</ref> 
{{Div col end}}

== See also ==
* [[leukocyte adhesion deficiency]]
* [[integrin]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Bunting M, Harris ES, McIntyre TM, Prescott SM, Zimmerman GA | title = Leukocyte adhesion deficiency syndromes: adhesion and tethering defects involving beta 2 integrins and selectin ligands | journal = Current Opinion in Hematology | volume = 9 | issue = 1 | pages = 30–5 | date = January 2002 | pmid = 11753075 | doi = 10.1097/00062752-200201000-00006 }}
* {{cite journal | vauthors = Roos D, Law SK | title = Hematologically important mutations: leukocyte adhesion deficiency | journal = Blood Cells, Molecules & Diseases | volume = 27 | issue = 6 | pages = 1000–4 | year = 2003 | pmid = 11831866 | doi = 10.1006/bcmd.2001.0473 }}
* {{cite journal | vauthors = Gahmberg CG, Fagerholm S | title = Activation of leukocyte beta2-integrins | journal = Vox Sanguinis | volume = 83 | pages = 355–8 | date = August 2002 | issue = Suppl 1 | pmid = 12617168 | doi = 10.1111/j.1423-0410.2002.tb05333.x | s2cid = 84695792 }}
* {{cite journal | vauthors = Schymeinsky J, Mócsai A, Walzog B | title = Neutrophil activation via beta2 integrins (CD11/CD18): molecular mechanisms and clinical implications | journal = Thrombosis and Haemostasis | volume = 98 | issue = 2 | pages = 262–73 | date = August 2007 | pmid = 17721605 | doi = 10.1160/th07-02-0156 | s2cid = 41094726 }}
{{refend}}

== External links ==
* {{MeshName|CD18+antigen}}
*[https://web.archive.org/web/20110722014120/http://cmkb.cellmigration.org/report.cgi?report=orth_overview&orth_acc=co00001789 ITGB2] Info with links in the [http://www.cellmigration.org/index.shtml Cell Migration Gateway] {{Webarchive|url=https://web.archive.org/web/20141211173306/http://www.cellmigration.org/index.shtml |date=11 December 2014 }}
* {{UCSC gene info|ITGB2}}

{{PDB Gallery|geneid=3689}}
{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{Complement system}}
{{Cell adhesion molecules}}
{{Integrins}}

{{Use dmy dates|date=April 2017}}

[[Category:Integrins]]
[[Category:Clusters of differentiation]]