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Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization
The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118065/ https://www.ncbi.nlm.nih.gov/pubmed/16401693 http://dx.doi.org/10.1084/jem.20050459 |
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author | Qin, Gangjian Ii, Masaaki Silver, Marcy Wecker, Andrea Bord, Evelyn Ma, Hong Gavin, Mary Goukassian, David A. Yoon, Young-sup Papayannopoulou, Thalia Asahara, Takayuki Kearney, Marianne Thorne, Tina Curry, Cynthia Eaton, Liz Heyd, Lindsay Dinesh, Deepika Kishore, Raj Zhu, Yan Losordo, Douglas W. |
author_facet | Qin, Gangjian Ii, Masaaki Silver, Marcy Wecker, Andrea Bord, Evelyn Ma, Hong Gavin, Mary Goukassian, David A. Yoon, Young-sup Papayannopoulou, Thalia Asahara, Takayuki Kearney, Marianne Thorne, Tina Curry, Cynthia Eaton, Liz Heyd, Lindsay Dinesh, Deepika Kishore, Raj Zhu, Yan Losordo, Douglas W. |
author_sort | Qin, Gangjian |
collection | PubMed |
description | The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs. |
format | Text |
id | pubmed-2118065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21180652007-12-13 Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization Qin, Gangjian Ii, Masaaki Silver, Marcy Wecker, Andrea Bord, Evelyn Ma, Hong Gavin, Mary Goukassian, David A. Yoon, Young-sup Papayannopoulou, Thalia Asahara, Takayuki Kearney, Marianne Thorne, Tina Curry, Cynthia Eaton, Liz Heyd, Lindsay Dinesh, Deepika Kishore, Raj Zhu, Yan Losordo, Douglas W. J Exp Med Articles The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs. The Rockefeller University Press 2006-01-23 /pmc/articles/PMC2118065/ /pubmed/16401693 http://dx.doi.org/10.1084/jem.20050459 Text en Copyright © 2006, 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 | Articles Qin, Gangjian Ii, Masaaki Silver, Marcy Wecker, Andrea Bord, Evelyn Ma, Hong Gavin, Mary Goukassian, David A. Yoon, Young-sup Papayannopoulou, Thalia Asahara, Takayuki Kearney, Marianne Thorne, Tina Curry, Cynthia Eaton, Liz Heyd, Lindsay Dinesh, Deepika Kishore, Raj Zhu, Yan Losordo, Douglas W. Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title | Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title_full | Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title_fullStr | Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title_full_unstemmed | Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title_short | Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
title_sort | functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118065/ https://www.ncbi.nlm.nih.gov/pubmed/16401693 http://dx.doi.org/10.1084/jem.20050459 |
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