インテグリンα4β1
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2014/04/01 10:11:13」(JST)
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Integrin alpha4beta1 (Very Late Antigen-4) is an integrin dimer. It is composed of CD49d (alpha 4) and CD29 (beta 1).
Vascular cell adhesion molecule-1 (VCAM-1 - an integrin receptor) located on an endothelial cell, binds to the integrin VLA-4 which are normally expressed on leukocyte plasma membranes, but they do not adhere to their appropriate ligands until the leukocytes are activated by chemotactic agents or other stimuli (often produced by the endothelium or other cells at the site of injury). Only then do the integrins undergo the conformational change necessary to confer high binding affinity for the endothelial adhesion molecules.
In multiple sclerosis, the VLA-4 integrin is essential in the processes by which T-cells gain access to the brain by allowing the cells to penetrate the blood brain barrier that normally restricts immune cell access. One approach to prevent an autoimmune reaction has been to block the action of VLA-4 so that self-reactive T-cells are unable to enter the brain and thus unable to attack myelin protein.[1]
In recent years antagonists of VLA-4 have shown great promise in treating inflammatory disorders in a number of animal models.[2] However, the usage of Natalizumab, an antagonist of VLA-4 integrin, remains controversial due to several side effects including Progressive multifocal leukoencephalopathy.
References[edit]
- ^ Paul, William E. (September 1993). "Infectious Diseases and the Immune System". Scientific American: 111–114.
- ^ Lin, Ko-Chung; Castro, Alfredo C. "Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents". Current Opinion in Chemical Biology 2 (4): 453–457. doi:10.1016/S1367-5931(98)80120-8.
External links[edit]
- Integrin alpha4beta1 at the US National Library of Medicine Medical Subject Headings (MeSH)
- ITGA4 ITGB1 Info with links in the Cell Migration Gateway
Membrane proteins: cell adhesion molecules
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Calcium-independent |
IgSF CAM |
- N-CAM (Myelin protein zero)
- ICAM (1, 5)
- VCAM-1
- PE-CAM
- L1-CAM
- Nectin (PVRL1, PVRL2, PVRL3)
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Integrins |
- LFA-1 (CD11a+CD18)
- Integrin alphaXbeta2 (CD11c+CD18)
- Macrophage-1 antigen (CD11b+CD18)
- VLA-4 (CD49d+CD29)
- Glycoprotein IIb/IIIa (ITGA2B+ITGB3)
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Calcium-dependent |
Cadherins |
Classical |
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Desmosomal |
- Desmoglein (DSG1, DSG2, DSG3, DSG4)
- Desmocollin (DSC1, DSC2, DSC3)
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Protocadherin |
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Unconventional/ungrouped |
- T-cadherin
- CDH4
- CDH5
- CDH6
- CDH8
- CDH11
- CDH12
- CDH15
- CDH16
- CDH17
- CDH9
- CDH10
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Selectins |
- E-selectin
- L-selectin
- P-selectin
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Other |
- Lymphocyte homing receptor: CD44
- L-selectin
- integrin (VLA-4, LFA-1)
- Carcinoembryonic antigen
- CD22
- CD24
- CD44
- CD146
- CD164
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- See also
- cell membrane protein disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), other
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Integrins
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Alpha |
- A1
- A2
- A3
- A4
- A5
- A6
- A7
- A8
- A9
- A10
- A11
- AD
- AE
- AL
- AM
- AV
- AX
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Beta |
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Dimers |
Cytoadhesin receptor: |
- Integrin alpha6beta4
- Glycoprotein IIb/IIIa
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Fibrinogen receptor: |
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Fibronectin receptor: |
- Integrin alpha2beta1
- Integrin alpha4beta1
- Integrin alpha5beta1
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Leukocyte-adhesion receptor: |
- LFA-1
- Macrophage-1 antigen
- Integrin alphaXbeta2
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Very late antigen receptor: |
- Integrin alpha1beta1
- Integrin alpha2beta1
- Integrin alpha3beta1
- VLA-4
- Alpha-5 beta-1
- Integrin alpha6beta1
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Vitronectin receptor: |
- Alpha-v beta-3
- Alpha-v beta-5
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see also cell surface receptor deficiencies
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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UpToDate Contents
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English Journal
- Progressive multifocal leukoencephalopathy in multiple sclerosis.
- Chalkley JJ, Berger JR.SourceDepartment of Neurology, University of Kentucky College of Medicine, 740 S. Limestone St., Room L-445, Lexington, KY, 40536-0284, USA, josh.chalkley@uky.edu.
- Current neurology and neuroscience reports.Curr Neurol Neurosci Rep.2013 Dec;13(12):408. doi: 10.1007/s11910-013-0408-6.
- AIDS generated a significantly increased interest in the pathogenesis, clinical manifestations, and treatment of progressive multifocal leukoencephalopathy (PML), a disease previously considered to be very rare. Scrutiny increased after a second wave of PML following the introduction of biological a
- PMID 24136456
- Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice.
- Sugiura T, Kageyama S, Andou A, Miyazawa T, Ejima C, Nakayama A, Dohi T, Eda H.SourceAjinomoto Pharmaceuticals Co., Ltd, Kawasaki, Japan.
- Journal of Crohn's & colitis.J Crohns Colitis.2013 Dec 1;7(11):e533-42. doi: 10.1016/j.crohns.2013.03.014. Epub 2013 Apr 24.
- BACKGROUND AND AIMS: Inhibition of lymphocyte trafficking by treatment with an anti-α4 integrin antibody has been clinically validated as a therapeutic approach for inflammatory bowel disease (IBD), and the orally effective 'anti-α4 integrin therapy' may be more convenient in clinical practice. Th
- PMID 23623333
- Vedolizumab, a monoclonal antibody to the gut homing α4β7 integrin, does not affect cerebrospinal fluid T-lymphocyte immunophenotype.
- Milch C, Wyant T, Xu J, Parikh A, Kent W, Fox I, Berger J.SourceMillennium Pharmaceuticals, Inc., a Takeda Company, 35 Landsdowne St., Cambridge, MA 02139, USA.
- Journal of neuroimmunology.J Neuroimmunol.2013 Nov 15;264(1-2):123-6. doi: 10.1016/j.jneuroim.2013.08.011. Epub 2013 Aug 31.
- Vedolizumab, a gut-homing α4β7 integrin antagonist, has demonstrated efficacy in ulcerative colitis and Crohn's disease. Development of progressive multifocal leukoencephalopathy, a serious brain infection associated with natalizumab (an α4β7 and α4β1 integrin antagonist), has raised concern t
- PMID 24067534
Japanese Journal
- Integrin alpha4beta1 involvement in stromal cell-derived factor-1alpha-promoted myeloma cell transendothelial migration and adhesion : role of cAMP and the actin cytoskeleton in adhesion
- Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways
Related Links
- "Integrin alpha4beta1" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings). Descriptors are ... Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present ...
- Integrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR ...
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インテグリン
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- integrins