Cargando…

Importance of integrin LFA-1 deactivation for the generation of immune responses

The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen–1 (LF...

Descripción completa

Detalles Bibliográficos
Autores principales: Semmrich, Monika, Smith, Andrew, Feterowski, Carolin, Beer, Sandra, Engelhardt, Britta, Busch, Dirk H., Bartsch, Bernadett, Laschinger, Melanie, Hogg, Nancy, Pfeffer, Klaus, Holzmann, Bernhard
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212031/
https://www.ncbi.nlm.nih.gov/pubmed/15955836
http://dx.doi.org/10.1084/jem.20041850
_version_ 1782148607881773056
author Semmrich, Monika
Smith, Andrew
Feterowski, Carolin
Beer, Sandra
Engelhardt, Britta
Busch, Dirk H.
Bartsch, Bernadett
Laschinger, Melanie
Hogg, Nancy
Pfeffer, Klaus
Holzmann, Bernhard
author_facet Semmrich, Monika
Smith, Andrew
Feterowski, Carolin
Beer, Sandra
Engelhardt, Britta
Busch, Dirk H.
Bartsch, Bernadett
Laschinger, Melanie
Hogg, Nancy
Pfeffer, Klaus
Holzmann, Bernhard
author_sort Semmrich, Monika
collection PubMed
description The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen–1 (LFA-1) α(L) subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1 (d/d) mutant mice showed constitutive activation of LFA-1–mediated cell adhesion and impaired de-adhesion from intercellular adhesion molecule-1 that resulted in defective cell migration. In contrast, signaling through LFA-1 was not affected in Lfa-1 (d/d) cells. T cell activation by superantigen-loaded and allogeneic APCs, cytotoxic T cell activity, T-dependent humoral immune responses, and neutrophil recruitment during aseptic peritonitis were impaired in Lfa-1 (d/d) mice. Thus, deactivation of LFA-1 and disassembly of LFA-1–mediated cell contacts seem to be vital for the generation of normal immune responses.
format Text
id pubmed-2212031
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-22120312008-03-11 Importance of integrin LFA-1 deactivation for the generation of immune responses Semmrich, Monika Smith, Andrew Feterowski, Carolin Beer, Sandra Engelhardt, Britta Busch, Dirk H. Bartsch, Bernadett Laschinger, Melanie Hogg, Nancy Pfeffer, Klaus Holzmann, Bernhard J Exp Med Article The dynamic regulation of ligand binding is considered crucial for integrin function. However, the importance of activity regulation for integrin function in vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR sequence of the lymphocyte function-associated antigen–1 (LFA-1) α(L) subunit cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1 (d/d) mutant mice showed constitutive activation of LFA-1–mediated cell adhesion and impaired de-adhesion from intercellular adhesion molecule-1 that resulted in defective cell migration. In contrast, signaling through LFA-1 was not affected in Lfa-1 (d/d) cells. T cell activation by superantigen-loaded and allogeneic APCs, cytotoxic T cell activity, T-dependent humoral immune responses, and neutrophil recruitment during aseptic peritonitis were impaired in Lfa-1 (d/d) mice. Thus, deactivation of LFA-1 and disassembly of LFA-1–mediated cell contacts seem to be vital for the generation of normal immune responses. The Rockefeller University Press 2005-06-20 /pmc/articles/PMC2212031/ /pubmed/15955836 http://dx.doi.org/10.1084/jem.20041850 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Semmrich, Monika
Smith, Andrew
Feterowski, Carolin
Beer, Sandra
Engelhardt, Britta
Busch, Dirk H.
Bartsch, Bernadett
Laschinger, Melanie
Hogg, Nancy
Pfeffer, Klaus
Holzmann, Bernhard
Importance of integrin LFA-1 deactivation for the generation of immune responses
title Importance of integrin LFA-1 deactivation for the generation of immune responses
title_full Importance of integrin LFA-1 deactivation for the generation of immune responses
title_fullStr Importance of integrin LFA-1 deactivation for the generation of immune responses
title_full_unstemmed Importance of integrin LFA-1 deactivation for the generation of immune responses
title_short Importance of integrin LFA-1 deactivation for the generation of immune responses
title_sort importance of integrin lfa-1 deactivation for the generation of immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212031/
https://www.ncbi.nlm.nih.gov/pubmed/15955836
http://dx.doi.org/10.1084/jem.20041850
work_keys_str_mv AT semmrichmonika importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT smithandrew importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT feterowskicarolin importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT beersandra importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT engelhardtbritta importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT buschdirkh importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT bartschbernadett importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT laschingermelanie importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT hoggnancy importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT pfefferklaus importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses
AT holzmannbernhard importanceofintegrinlfa1deactivationforthegenerationofimmuneresponses