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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...

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Autores principales: 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.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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