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23-474: 3383 15894 ENSG00000090339 ENSMUSG00000037405 P05362 P13597 NM_000201 NM_010493 NP_000192 NP_034623 ICAM-1 ( Intercellular Adhesion Molecule 1) also known as CD54 ( C luster of D ifferentiation 54) is a protein that in humans is encoded by the ICAM1 gene . This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of

46-472: A receptor found on leukocytes. When activated, leukocytes bind to endothelial cells via ICAM-1/ LFA-1 and then transmigrate into tissues. LFA-1 has also been found in a soluble form, which seems to bind and block ICAM-1. ICAM-1 is an endothelial - and leukocyte -associated transmembrane protein long known for its importance in stabilizing cell-cell interactions and facilitating leukocyte endothelial transmigration. More recently, ICAM-1 has been characterized as

69-416: A recruitment of inflammatory immune cells such as macrophages and granulocytes. ICAM-1 may also participate in a positive feedback loop and compete with ICAM-2 to maintain a proinflammatory environment conducive to leukocyte endothelial transmigration. At both the mRNA and protein levels of expression, ICAM-1 ligation was found to upregulate ICAM-1’s own expression in a positive-feedback loop. In addition,

92-439: A role for ICAM-1 in infectious disease. With the roles of ICAM-1 in cell-cell adhesion, extravasation, and infection more fully understood, a potential role for ICAM-1 in signal transduction was hypothesized. Most of the work involving ICAM-1 in recent years has focused on this central question as well as related questions. Researchers reasoned that, should ICAM-1 signal transduction prove to occur, it would be necessary to identify

115-502: A single transmembrane domain, and a carboxy-terminus cytoplasmic domain. The structure of ICAM-1 is characterized by heavy glycosylation , and the protein’s extracellular domain is composed of multiple loops created by disulfide bridges within the protein. The dominant secondary structure of the protein is the beta sheet , leading researchers to hypothesize the presence of dimerization domains within ICAM-1. The protein encoded by this gene

138-424: A site for the cellular entry of human rhinovirus . Because of these associations with immune responses, it has been hypothesized that ICAM-1 could function in signal transduction. ICAM-1 ligation produces proinflammatory effects such as inflammatory leukocyte recruitment by signaling through cascades involving a number of kinases, including the kinase p56lyn . ICAM-1 and soluble ICAM-1 have antagonistic effects on

161-469: A study linking ICAM signaling to actual modulation of an inflammatory environment in vivo has yet to be conducted. The reticular nature of signaling cascades necessitates that the downstream effectors of ICAM-1 mediated signaling through various kinases including p56lyn , Raf-1 , and the MAPKs are largely unknown. A more thorough study of the cross-talk between these signaling molecules may shed further light onto

184-488: Is a stub . You can help Misplaced Pages by expanding it . CD18 1L3Y , 1YUK , 2JF1 , 2P26 , 2P28 , 3K6S , 3K71 , 3K72 , 2V7D , 4NEH , 4NEN , 5E6X , 5E6V , 5E6S , 5E6R , 5E6W , 5ES4 , 5E6U 3689 16414 ENSG00000160255 ENSMUSG00000000290 P05107 P11835 NM_000211 NM_001127491 NM_001303238 NM_008404 NP_000202 NP_001120963 NP_001290167 NP_032430 In molecular biology, CD18 ( Integrin beta chain-2 )

207-419: Is a type of intercellular adhesion molecule continuously present in low concentrations in the membranes of leukocytes and endothelial cells . Upon cytokine stimulation, the concentrations greatly increase. ICAM-1 can be induced by interleukin-1 (IL-1) and tumor necrosis factor (TNF) and is expressed by the vascular endothelium, macrophages , and lymphocytes . ICAM-1 is a ligand for LFA-1 ( integrin ),

230-580: 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. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing

253-401: The immune system . It binds to integrins of type CD11a / CD18 , or CD11b / CD18 and is also exploited by rhinovirus as a receptor for entry into respiratory epithelium . ICAM-1 is a member of the immunoglobulin superfamily , the superfamily of proteins including antibodies and T-cell receptors . ICAM-1 is a transmembrane protein possessing an amino-terminus extracellular domain,

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276-586: The immunoglobulin superfamily . They are important in inflammation , immune responses and in intracellular signalling events. The ICAM family consists of five members, designated ICAM-1 to ICAM-5. They are known to bind to leucocyte integrins CD11 / CD18 such as LFA-1 and Macrophage-1 antigen , during inflammation and in immune responses. In addition, ICAMs may exist in soluble forms in human plasma , due to activation and proteolysis mechanisms at cell surfaces. Mammalian intercellular adhesion molecules include: This biochemistry article

299-410: The innate immune response by recognizing foreign antigen peptides and phagocytizing them, thus destroying the antigen. 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

322-687: The tight junctions forming the blood-testis barrier , thus playing a major role in spermatogenesis . The presence of heavy glycosylation and other structural characteristics of ICAM-1 lend the protein binding sites for numerous ligands. ICAM-1 possesses binding sites for a number of immune-associated ligands. Notably, ICAM-1 binds to macrophage adhesion ligand-1 (Mac-1; ITGB2 / ITGAM ), l eukocyte f unction associated antigen-1 ( LFA-1 ), and fibrinogen . These three proteins are generally expressed on endothelial cells and leukocytes, and they bind to ICAM-1 to facilitate transmigration of leukocytes across vascular endothelia in processes such as extravasation and

345-496: 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

368-433: The biological endpoints produced by ICAM-1 ligation and signal transduction. ICAM-1 has been implicated in subarachnoid hemorrhage (SAH). Levels of ICAM-1 are shown to be significantly elevated in patients with SAH over control subjects in many studies. While ICAM-1 has not been shown to be directly correlated with cerebral vasospasm , a secondary symptom that affects 70% of SAH patients, treatment with anti-ICAM-1 reduced

391-514: The expression of RANTES mRNA and protein was also found to be upregulated by ICAM-1 ligation. RANTES, or Regulated upon Activation Normal T-cell Expressed and Secreted, is a cytokine that is an inflammatory mediator chemotactic for a variety of inflammatory immune cells such as granulocytes and macrophages. However, much work remains to be done in fully characterizing the signaling of ICAM-1. The relationship between ICAM-1 and ICAM-2 signaling environments has not been established beyond mere correlation;

414-603: 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

437-607: The immune system's ability to fight off foreign invaders. 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

460-421: The induction of ICAM-1 and VCAM-1 surface expression in human brain tissues and primary human brain endothelial cells (BMVEC) exposed to various pro-inflammatory mediators. ICAM-1 has been shown to interact with CD11a , EZR and CD18 . Intercellular adhesion molecule In molecular biology , intercellular adhesion molecules ( ICAMs ) and vascular cell adhesion molecule-1 (VCAM-1) are part of

483-581: The inflammatory response. As a result of these binding characteristics, ICAM-1 has classically been assigned the function of intercellular adhesion . Researchers began to question the role of ICAM-1 as a simple adhesion molecule upon discovering that ICAM-1 serves as the binding site for entry of the major group of human rhinovirus ( HRV ) into various cell types. ICAM-1 also became known for its affinity for Plasmodium falciparum -infected erythrocytes (PFIE), acting synergistically in mediating adherence of PFIE to endothelium co-expressing CD36 , providing more of

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506-508: The mechanism of that signaling, the conditions and environment in which the signaling would occur, and the biological endpoints of any signaling cascades involved. Beyond its classically described functions as an adhesion and viral entry molecule, ICAM-1 has now been characterized convincingly as possessing a role in signal transduction. Furthermore, the signal-transducing functions of ICAM-1 seem to be associated primarily with proinflammatory pathways. In particular, ICAM-1 signaling seems to produce

529-531: The severity of vasospasm. ICAM-1 expressed by respiratory epithelial cells is also the binding site for rhinovirus , the causative agent of most common colds . ICAM-1 has an important role in ocular allergies recruiting pro-inflammatory lymphocytes and mast cells promoting a type I hypersensitivity reaction. ICAM-1 is the primary entry receptor for Coxsackievirus A21, an oncolytic virus (brand name Cavatak, being developed by Viralytics ). Cannabinoid CB2 receptor agonists have been found to decrease

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