The Journal of Experimental Medicine
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 12 September 2005 doi:10.1084/jem.20050959
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 6, 739-750
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Heissig, B.
Right arrow Articles by Hattori, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heissig, B.
Right arrow Articles by Hattori, K.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Low-dose irradiation promotes tissue revascularization through VEGF release from mast cells and MMP-9–mediated progenitor cell mobilization

Beate Heissig1,2, Shahin Rafii3, Haruyo Akiyama1, Yuichi Ohki1, Yayoi Sato1, Tejada Rafael3, Zhenping Zhu4, Daniel J. Hicklin4, Ko Okumura2, Hideoki Ogawa2, Zena Werb5, and Koichi Hattori1,2

1 Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan
2 Atopy (Allergy) Research Center, Juntendo University School of Medicine, Tokyo, 113-8421, Japan
3 Department of Hematology-Oncology Cornell University Medical College, New York, NY 10021
4 ImClone Systems, New York, NY 10014
5 Department of Anatomy, University of California, San Francisco, CA 94143

CORRESPONDENCE Koichi Hattori: hattoriko{at}yahoo.com

Mast cells accumulate in tissues undergoing angiogenesis during tumor growth, wound healing, and tissue repair. Mast cells can secrete angiogenic factors such as vascular endothelial growth factor (VEGF). Ionizing irradiation has also been shown to have angiogenic potential in malignant and nonmalignant diseases. We observed that low-dose irradiation fosters mast cell–dependent vascular regeneration in a limb ischemia model. Irradiation promoted VEGF production by mast cells in a matrix metalloproteinase-9 (MMP-9)–dependent manner. Irradiation, through MMP-9 up-regulated by VEGF in stromal and endothelial cells, induced the release of Kit-ligand (KitL). Irradiation-induced VEGF promoted migration of mast cells from the bone marrow to the ischemic site. Irradiation-mediated release of KitL and VEGF was impaired in MMP-9–deficient mice, resulting in a reduced number of tissue mast cells and delayed vessel formation in the ischemic limb. Irradiation-induced vasculogenesis was abrogated in mice deficient in mast cells (steel mutant, Sl/Sld mice) and in mice in which the VEGF pathway was blocked. Irradiation did not induce progenitor mobilization in Sl/Sld mice. We conclude that increased recruitment and activation of mast cells following irradiation alters the ischemic microenvironment and promotes vascular regeneration in an ischemia model. These data show a novel mechanism of neovascularization and suggest that low-dose irradiation may be used for therapeutic angiogenesis to augment vasculogenesis in ischemic tissues.

Abbreviations used: BMNC, BM mononuclear cell; CEP, circulating endothelial progenitor; CFU-C, CFU cell; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; HL, hind limb; IR, irradiation; KitL, Kit-ligand; MCP, monocyte chemotactic protein; MMP, matrix metalloproteinase; MPI, matrix metalloproteinase inhibitor; NO, nitric oxide; PlGF, placental growth factor; rVEGF, recombinant vascular endothelial growth factor; SDF, stromal cell–derived factor; SMA, smooth muscle actin; SMC, smooth muscle cell; TBI, total body irradiation; TGF, transforming growth factor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; vWF, von Willebrand factor.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Vessel-building mast cells
Heather L. Van Epps
J. Exp. Med. 2005 202: 725. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS