Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut.

Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Research Abstract Details 

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Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Abstract Text:

Ivor S Douglas,Themistocles Dassopoulos,

Integrin adhesion molecules mediate lymphocyte migration and homing to normal and inflamed tissues. While the ligand-binding activity of integrins is known to be modulated by conformational changes, little is known about how the appropriate balance of integrin adhesiveness is maintained in order to optimize the migratory capacity of lymphocytes in vivo. In this study we examined the regulation of the gut homing receptor alpha4beta7 integrin by manipulating at the germline level an integrin regulatory domain known as adjacent to metal ion-dependent adhesion site (ADMIDAS). ADMIDAS normally serves to raise the activation threshold of alpha4beta7, thereby stabilizing it in the default nonadhesive state. Lymphocytes from knockin beta7 (D146A) mice, which harbor a disrupted ADMIDAS, not only expressed an alpha4beta7 integrin that persistently adhered to mucosal addressin cell adhesion molecule-1 (MAdCAM-1), but also exhibited perturbed cell migration along MAdCAM-1 substrates resulting from improper de-adhesion of the lymphocyte trailing edge. In vivo, aberrantly activated alpha4beta7 enhanced adhesion to Peyer's patch venules, but suppressed lymphocyte homing to the gut, diminishing the capacity of T cells to induce colitis. Our results underscore the importance of a proper balance in the adhesion and de-adhesion of the alpha4beta7 integrin, both for lymphocyte trafficking to the gut and for colitis progression.

Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Publishing Authors By Initials

IS Douglas,T Dassopoulos,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: protein binding research

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Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 2526-38

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 3

MONTH: Sep

YEAR: 2007

Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Keywords Mesh Terms:

KEYWORDS: Protein Binding

MESH TERMS: genetics

Chemical & Substance for Abstract: Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut. Information

Substance Name: Aspartic Acid

Registry Number: 56-84-8

Grant and Affiliation Information for Aberrant activation of integrin alpha4beta7 suppresses lymphocyte migration to the gut.

AFFILIATION: CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL048675

ACRONYM: HL

MEDLINETA: J Clin Invest

REFSOURCE: J Clin Invest. 2007 Sep;117(9):2391-5

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