Wikipedia preview

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)

wiki en

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. Cite uses deprecated parameters (help)

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

This immunology article is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 炎症の病因における白血球内皮細胞接着 leukocyte endothelial adhesion in the pathogenesis of inflammation
2. Leukocyte-adhesion deficiency
3. 成人におけるステロイド抵抗性およびステロイド依存性の潰瘍性大腸炎に対するアプローチ approach to adults with steroid refractory and steroid dependent ulcerative colitis
4. 鎌状細胞貧血における臨床的ばらつき clinical variability in sickle cell anemia
5. 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

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

PARMO-CABANAS M
Exp Cell Res 294, 571-580, 2004
NAID 30018229870

Lymphocyte homing to bronchus-associated lymphoid tissue (BALT) is mediated by L-selectin/PNAd, alpha4beta1 integrin/VCAM-1, and LFA-1 adhesion pathways