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a fibrous band of scar tissue that binds together normally separate anatomical structures
abnormal union of bodily tissues; most common in the abdomen
(physics and chemistry) the simplest structural unit of an element or compound
located between cells

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粘着,付着
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細胞間の,細胞間にある

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/10 16:54:16」(JST)

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ICAM-1 (Intercellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) is a protein that in humans is encoded by the ICAM1 gene.^[1]^[2] This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system. It binds to integrins of type CD11a / CD18, or CD11b / CD18 and is also exploited by rhinovirus as a receptor.^[3]

Structure

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, 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.^[4]

Function

The protein encoded by this gene 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), a receptor found on leukocytes.^[5] When activated, leukocytes bind to endothelial cells via ICAM-1/LFA-1 and then transmigrate into tissues.^[6]

Role in cell signaling

ICAM-1 (Intercellular Adhesion Molecule-1, CD54) 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 a site for the cellular entry of human rhinovirus.^[7] 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.

Other functions

ICAM-1 and soluble ICAM-1 have antagonistic effects on the tight junctions forming the blood-testis barrier, thus playing a major role in spermatogenesis.^[8]

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), leukocyte function 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 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.^[4] ICAM-1 also became known for its affinity for plasmodium falciparum-infected erythrocytes (PFIE), providing more of 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 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 a recruitment of inflammatory immune cells such as macrophages and granulocytes.^[9]

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, 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.^[10] 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; 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 the biological endpoints produced by ICAM-1 ligation and signal transduction.

Clinical significance

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.^[11]^[12] 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 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.

Interactions

ICAM-1 has been shown to interact with CD11a,^[13]^[14]^[15] EZR^[16] and CD18.^[13]^[17]^[18]

References

^ Carlson M, Nakamura Y, Payson R, O'Connell P, Leppert M, Lathrop GM, Lalouel JM, White R (May 1988). "Isolation and mapping of a polymorphic DNA sequence (pMCT108.2) on chromosome 18 D18S24". Nucleic Acids Res. 16 (9): 4188. doi:10.1093/nar/16.9.4188. PMC 336612. PMID 2453850.
^ Katz FE, Parkar M, Stanley K, Murray LJ, Clark EA, Greaves MF (January 1985). "Chromosome mapping of cell membrane antigens expressed on activated B cells". Eur. J. Immunol. 15 (1): 103–6. doi:10.1002/eji.1830150121. PMID 3871395.
^ "Entrez Gene: intercellular adhesion molecule 1".
^ ^a ^b Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG (April 1998). "The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand". Proc. Natl. Acad. Sci. U.S.A. 95 (8): 4140–5. doi:10.1073/pnas.95.8.4140. PMC 22455. PMID 9539703.
^ Rothlein, R. D. (Aug 1986). "A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1". Journal of Immunology 137 (4): 1270–1274. ISSN 0022-1767. PMID 3525675. edit
^ Yang L, Froio RM, Sciuto TE, Dvorak AM, Alon R, Luscinskas FW (July 2005). "ICAM-1 regulates neutrophil adhesion and transcellular migration of TNF-α-activated vascular endothelium under flow". Blood 106 (2): 584–92. doi:10.1182/blood-2004-12-4942. PMC 1635241. PMID 15811956.
^ Abraham G, Colonno RJ (August 1984). "Many rhinovirus serotypes share the same cellular receptor". J. Virol. 51 (2): 340–5. PMC 254443. PMID 6086949.
^ Xiao, X.; Mruk, D. D.; Cheng, C. Y. (2013). "Intercellular adhesion molecules (ICAMs) and spermatogenesis". Human Reproduction Update 19 (2): 167–186. doi:10.1093/humupd/dms049. PMC 3576004. PMID 23287428. edit
^ Etienne-Manneville S, Chaverot N, Strosberg AD, Couraud PO (July 1999). "ICAM-1-coupled signaling pathways in astrocytes converge to cyclic AMP response element-binding protein phosphorylation and TNF-alpha secretion". J. Immunol. 163 (2): 668–74. PMID 10395656.
^ Blaber R, Stylianou E, Clayton A, Steadman R (January 2003). "Selective regulation of ICAM-1 and RANTES gene expression after ICAM-1 ligation on human renal fibroblasts". J. Am. Soc. Nephrol. 14 (1): 116–27. doi:10.1097/01.ASN.0000040595.35207.62. PMID 12506144.
^ Polin RS, Bavbek M, Shaffrey ME, Billups K, Bogaev CA, Kassell NF, Lee KS (October 1998). "Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage". J. Neurosurg. 89 (4): 559–67. doi:10.3171/jns.1998.89.4.0559. PMID 9761049.
^ Frijns CJ, Kappelle LJ (August 2002). "Inflammatory cell adhesion molecules in ischemic cerebrovascular disease". Stroke 33 (8): 2115–22. doi:10.1161/01.STR.0000021902.33129.69. PMID 12154274.
^ ^a ^b Lu, C; Takagi J, Springer T A (May 2001). "Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state". J. Biol. Chem. (United States) 276 (18): 14642–8. doi:10.1074/jbc.M100600200. ISSN 0021-9258. PMID 11279101. Cite uses deprecated parameters (help)
^ Shimaoka, Motomu; Xiao Tsan, Liu Jin-Huan, Yang Yuting, Dong Yicheng, Jun Chang-Duk, McCormack Alison, Zhang Rongguang, Joachimiak Andrzej, Takagi Junichi, Wang Jia-Huai, Springer Timothy A (Jan 2003). "Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation". Cell (United States) 112 (1): 99–111. doi:10.1016/S0092-8674(02)01257-6. ISSN 0092-8674. PMID 12526797. Cite uses deprecated parameters (help)
^ Yusuf-Makagiansar, H; Makagiansar I T; Hu Y; Siahaan T J (Dec 2001). "Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction". Peptides (United States) 22 (12): 1955–62. doi:10.1016/S0196-9781(01)00546-0. ISSN 0196-9781. PMID 11786177.
^ Heiska, L; Alfthan K; Grönholm M; Vilja P; Vaheri A; Carpén O (Aug 1998). "Association of ezrin with intercellular adhesion molecule-1 and -2 (ICAM-1 and ICAM-2). Regulation by phosphatidylinositol 4, 5-bisphosphate". J. Biol. Chem. (UNITED STATES) 273 (34): 21893–900. doi:10.1074/jbc.273.34.21893. ISSN 0021-9258. PMID 9705328.
^ Kotovuori, A; Pessa-Morikawa T; Kotovuori P; Nortamo P; Gahmberg C G (Jun 1999). "ICAM-2 and a peptide from its binding domain are efficient activators of leukocyte adhesion and integrin affinity". J. Immunol. (UNITED STATES) 162 (11): 6613–20. ISSN 0022-1767. PMID 10352278.
^ Huang, C; Springer T A (Aug 1995). "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)". J. Biol. Chem. (UNITED STATES) 270 (32): 19008–16. doi:10.1074/jbc.270.32.19008. ISSN 0021-9258. PMID 7642561.

External links

Intercellular Adhesion Molecule-1 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 臨床的腎移植における研究中の免疫抑制剤およびそのアプローチ investigational immunosuppressive drugs and approaches in clinical kidney transplantation
2. クローン病の内科的マネージメントにおける試験研究治療 investigational therapies in the medical management of crohn disease
3. ライノウイルス感染の疫学、臨床症状、および病因 epidemiology clinical manifestations and pathogenesis of rhinovirus infections
4. Leukocyte-adhesion deficiency
5. ウイルス誘発性の喘鳴および喘息：概要 virus induced wheezing and asthma an overview

English Journal

Assessment of relationship on excess fluoride intake from drinking water and carotid atherosclerosis development in adults in fluoride endemic areas, China.

Liu H1, Gao Y1, Sun L1, Li M1, Li B1, Sun D2.Author information 1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618104), Harbin 150081, China.2Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China; Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618104), Harbin 150081, China. Electronic address: hrbmusdj@163.com.AbstractCross-sectional analysis was conducted to access the relationships between developing carotid artery atherosclerosis through consuming high fluoride in drinking water and its possible mechanism, using the baseline data collected from 585 study subjects. In the cross sectional analysis, subjects were divided into four groups based on the concentrations of fluoride in their drinking water. The range of fluoride concentrations was: normal group (less than 1.20mg/L), mild group (1.21-2.00mg/L), moderate group (2.01-3.00mg/L), and high concentration group (more than 3.01mg/L). The prevalence rate of carotid artery atherosclerosis in the subjects in each group was found to be 16.13%, 27.22%, 27.10%, and 29.69%, respectively. Significant difference between the prevalence of carotid artery atherosclerosis in the mild, moderate and high fluoride exposure group and in the normal group was observed (P<0.05). In addition, it was found that elevated intercellular cell adhesion molecule-1 (ICAM-1) and reduced glutathione peroxidases (GPx) was associated with carotid artery atherosclerosis in fluoride endemic areas. The findings of the research study revealed a significant positive relationship between excess fluoride exposure from drinking water and prevalence of carotid artery atherosclerosis in adults living in fluoride endemic areas. The possible mechanism was the excess fluoride induced the decreasing level of GPx causing the systemic inflammation and endothelial activation by oxidative stress.
International journal of hygiene and environmental health.Int J Hyg Environ Health.2014 Mar;217(2-3):413-20. doi: 10.1016/j.ijheh.2013.08.001. Epub 2013 Aug 14.
Cross-sectional analysis was conducted to access the relationships between developing carotid artery atherosclerosis through consuming high fluoride in drinking water and its possible mechanism, using the baseline data collected from 585 study subjects. In the cross sectional analysis, subjects were
PMID 24012047

Improved adhesion and differentiation of endothelial cells on surface-attached fibrin structures containing extracellular matrix proteins.

Filová E, Brynda E, Riedel T, Chlupáč J, Vandrovcová M, Svindrych Z, Lisá V, Houska M, Pirk J, Bačáková L.Author information Department of Biomaterials and Tissue Engineering, Institute of Physiology, Academy of Sciences of the Czech Republic, v.v.i., 142 20 Prague 4, Czech Republic.AbstractCurrently used vascular prostheses are hydrophobic and do not allow endothelial cell (EC) adhesion and growth. The aim of this study was to prepare fibrin (Fb)-based two-dimensional (2D) and three-dimensional (3D) assemblies coated with extracellular matrix (ECM) proteins and to evaluate the EC adhesion, proliferation and differentiation on these assemblies in vitro. Coating of Fb with collagen, laminin (LM), and fibronectin (FN) was proved using the surface plasmon resonance technique. On all Fb assemblies, ECs reached higher cell densities than on polystyrene after 3 and 7 days of culture. Immunoflurescence staining showed better assembly of talin and vinculin into focal adhesion plaques, and also more apparent staining of vascular endothelial cadherin on surface-attached 3D Fb and protein-coated Fb assemblies. On these samples, ECs also contained a lower concentration of intercellular adhesion molecule-1, measured by enzyme-linked immunosorbent assay. Higher concentrations of CD31 (platelet-endothelial cell adhesion molecule-1) were found on 3D Fb coated with LM, and higher concentrations of von Willebrand factor were found on 3D Fb coated with type I collagen or LM in comparison to 2D Fb layers. The results indicate that ECM protein-coated 2D and 3D Fb assemblies can be used for versatile applications in various tissue replacements where endothelialization is desirable, for example, vascular prostheses and heart valves. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 698-712, 2014.
Journal of biomedical materials research. Part A.J Biomed Mater Res A.2014 Mar;102(3):698-712. doi: 10.1002/jbm.a.34733. Epub 2013 May 30.
Currently used vascular prostheses are hydrophobic and do not allow endothelial cell (EC) adhesion and growth. The aim of this study was to prepare fibrin (Fb)-based two-dimensional (2D) and three-dimensional (3D) assemblies coated with extracellular matrix (ECM) proteins and to evaluate the EC adhe
PMID 23723042

Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease.

Yates CM1, Calder PC2, Ed Rainger G3.Author information 1Centre for Cardiovascular Sciences, School of Clinical and Experimental Medicine, The University of Birmingham, B15 2TT, UK.2Human Development & Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.3Centre for Cardiovascular Sciences, School of Clinical and Experimental Medicine, The University of Birmingham, B15 2TT, UK. Electronic address: g.e.rainger@bham.ac.uk.AbstractOmega-3 (n-3) polyunsaturated fatty acids (n-3 PUFAs) have well documented anti-inflammatory properties, and consequently therapeutic potential in chronic inflammatory diseases. Here we discuss the effects of n-3 PUFAs on various inflammatory pathways and how this leads to alterations in the function of inflammatory cells, most importantly endothelial cells and leukocytes. Strong evidence indicates n-3 PUFAs are beneficial as a dietary supplement in certain diseases such as rheumatoid arthritis; however for other conditions such as asthma, the data are less robust. A clearer understanding of the pharmacology of n-3 PUFAs will help to establish targets to modulate chronic inflammatory diseases.
Pharmacology & therapeutics.Pharmacol Ther.2014 Mar;141(3):272-82. doi: 10.1016/j.pharmthera.2013.10.010. Epub 2013 Nov 4.
Omega-3 (n-3) polyunsaturated fatty acids (n-3 PUFAs) have well documented anti-inflammatory properties, and consequently therapeutic potential in chronic inflammatory diseases. Here we discuss the effects of n-3 PUFAs on various inflammatory pathways and how this leads to alterations in the functio
PMID 24201219

Japanese Journal

3) 血管内皮から観た妊娠高血圧症候群の病態とその発症予知(シンポジウム2:周産期「妊娠高血圧症候群の基礎と臨床-予防・治療の新戦略に向けて」,第65回日本産科婦人科学会・学術講演会)

松原圭一
日本産科婦人科學會雜誌 65(11), 2591-2603, 2013-11-01
… Adhesion (rolling-adhesion) between leukocyte and endothelium is an important process for the beginning of inflammation and the expression of adhesion molecules is important on the cells. … On the other hand, intercellular adhesion molecule-1 (ICAM-1) was strongly expressed on endothelial cells by serum derived from PIH. …
NAID 110009661871

Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice(BREWING AND FOOD TECHNOLOGY)

Ueki Masaaki,Ueno Masaki,Morishita Jun,Maekawa Nobuhiro
Journal of bioscience and bioengineering 115(5), 547-551, 2013-05
… Serum and renal tumor necrosis factor (TNF)-alpha and renal monocyte chemoattractant protein (MCP)-1 concentrations, intercellular adhesion molecule-1 (ICAM-1) mRNA expression in kidney, renal function and histological changes were determined 72 h after cisplatin injection. …
NAID 110009611461

Impaired endothelium-dependent vasodilator response in patients with pulmonary fibrosis.

Aihara Kensaku,Handa Tomohiro,Nagai Sonoko,Tanizawa Kiminobu,Ikezoe Kohei,Watanabe Kizuku,Chihara Yuichi,Harada Yuka,Yoshimura Chikara,Oga Toru,Ozasa Neiko,Uno Kazuko,Chin Kazuo,Mishima Michiaki
Respiratory medicine 107(2), 269-275, 2013-02
… Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI. …
NAID 120005241355

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★リンクテーブル★

リンク元	「ICAM-1」
拡張検索	「intercellular adhesion molecule-1」
関連記事	「adhesion」「molecule」「intercellular」

「ICAM-1」

Intercellular adhesion molecule 1
	; PDB rendering based on 1d3e.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1D3E, 1D3I, 1D3L, 1IAM, 1IC1, 1IJ4, 1MQ8, 1P53, 1Z7Z, 2OZ4, 3TCX
Identifiers
Symbols	ICAM1 ; BB2; CD54; P3.58
External IDs	OMIM: 147840 MGI: 96392 HomoloGene: 168 ChEMBL: 3070 GeneCards: ICAM1 Gene
Gene ontology
Molecular function	• virus receptor activity; • receptor activity; • transmembrane signaling receptor activity; • integrin binding; • protein binding;
Cellular component	• immunological synapse; • extracellular space; • plasma membrane; • integral component of plasma membrane; • external side of plasma membrane; • membrane; • extracellular vesicular exosome;
Biological process	• ovarian follicle development; • regulation of leukocyte mediated cytotoxicity; • response to amphetamine; • T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; • T cell antigen processing and presentation; • positive regulation of cellular extravasation; • cell adhesion; • heterophilic cell-cell adhesion; • leukocyte cell-cell adhesion; • cell aging; • regulation of cell shape; • response to virus; • response to ionizing radiation; • response to sulfur dioxide; • response to organic cyclic compound; • cytokine-mediated signaling pathway; • membrane to membrane docking; • regulation of cell adhesion; • extracellular matrix organization; • positive regulation of actin filament polymerization; • cellular response to nutrient levels; • positive regulation of Rho GTPase activity; • cell adhesion mediated by integrin; • response to gonadotropin; • response to drug; • response to amino acid; • adhesion of symbiont to host; • positive regulation of nitric oxide biosynthetic process; • response to ethanol; • positive regulation of vasoconstriction; • response to copper ion; • receptor-mediated virion attachment to host cell; • positive regulation of peptidyl-tyrosine phosphorylation; • regulation of immune response; • leukocyte migration; • positive regulation of NF-kappaB transcription factor activity; • negative regulation of calcium ion transport; • interferon-gamma-mediated signaling pathway; • establishment of endothelial barrier; • positive regulation of ERK1 and ERK2 cascade; • cellular response to lipopolysaccharide; • cellular response to alkaloid; • cellular response to glucose stimulus; • cellular response to interleukin-1; • cellular response to tumor necrosis factor; • cellular response to hypoxia; • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; • negative regulation of endothelial cell apoptotic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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