Contribution of Macrophages to Angiogenesis Induced by Vascular Endothelial Growth Factor Receptor-3-Specific Ligands
- Authors
- Chung, ES[Chung, Eui-Sang]; Chauhan, SK[Chauhan, Sunil Kumar]; Jin, YP[Jin, Yiping]; Nakao, S[Nakao, Shintaro]; Hafezi-Moghadam, A[Hafezi-Moghadam, Ali]; van Rooijen, N[van Rooijen, Nico]; Zhang, Q[Zhang, Qiang]; Chen, L[Chen, Lu]; Dana, R[Dana, Reza]
- Issue Date
- Nov-2009
- Publisher
- AMER SOC INVESTIGATIVE PATHOLOGY, INC
- Citation
- AMERICAN JOURNAL OF PATHOLOGY, v.175, no.5, pp.1984 - 1992
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF PATHOLOGY
- Volume
- 175
- Number
- 5
- Start Page
- 1984
- End Page
- 1992
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/76749
- DOI
- 10.2353/ajpath.2009.080515
- ISSN
- 0002-9440
- Abstract
- Vascular endothelial growth factor receptor (VEGFR)-2 is a major stimulator of hemangiogenesis (HA), whereas VEGFR-3 stimulates lymphangiogenesis (LA). Contrary to this understanding, we demonstrate that implantation of pellets containing VEGFR-3-specific ligands (VEGF-C156S and recombinant murine VEGF-D) into the corneal stroma induce not only LA but also robust HA characterized by blood vessels that are positive for VEGFR-3 expression. The implantation of pellets containing VEGFR-3-specific ligands also leads to the recruitment of VEGF-A-secreting macrophages. Depletion of these infiltrating macrophages using clodronate-liposome administration shows a significant reduction in HA as well as LA. Blockade of either VEGFR-2 or VEGFR-3 signaling reduces both HA and LA; however, the percent reduction of HA is greater in the VEGFR-2 blockade group. In addition, in the VEGFR-3 blockade group, the percent reduction of RA is significantly greater with VEGFR-3-specific ligands than that by VEGF-A or VEGF-C. Collectively, our data suggest that VEGFR-3-specific signaling can induce new blood vessels, to which macrophages contribute a major role, and signify its potential as an additional therapeutic target to the existing VEGF-A/VEGFR-2 signaling-based antiangiogenesis strategies. (Am J Pathol 2009, 175:1984-1992; DOI: 10.2353/ajpath.2009.080515)
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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