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Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2011 May 09; Vol. 208 (5), pp. 1083-92. Date of Electronic Publication: 2011 May 02. - Publication Year :
- 2011
-
Abstract
- Lymphangiogenesis plays an important role in tumor metastasis and transplant outcome. Here, we show that thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein and naturally occurring inhibitor of angiogenesis inhibits lymphangiogenesis in mice. Compared with wild-type mice, 6-mo-old TSP-1-deficient mice develop increased spontaneous corneal lymphangiogenesis. Similarly, in a model of inflammation-induced corneal neovascularization, young TSP-1-deficient mice develop exacerbated lymphangiogenesis, which can be reversed by topical application of recombinant human TSP-1. Such increased corneal lymphangiogenesis is also detected in mice lacking CD36, a receptor for TSP-1. In these mice, repopulation of corneal macrophages with predominantly WT mice via bone marrow reconstitution ameliorates their prolymphangiogenic phenotype. In vitro, exposure of WT macrophages to TSP-1 suppresses expression of lymphangiogenic factors vascular endothelial growth factor (VEGF)-C and VEGF-D, but not of a primarily hemangiogenic factor VEGF-A. Inhibition of VEGF-C is not detected in the absence or blockade of CD36. These findings suggest that TSP-1, by ligating CD36 on monocytic cells, acts as an endogenous inhibitor of lymphangiogenesis.
- Subjects :
- Animals
CD36 Antigens genetics
CD36 Antigens immunology
Cornea immunology
Cornea metabolism
Cornea pathology
Corneal Neovascularization genetics
Corneal Neovascularization immunology
Corneal Neovascularization metabolism
Corneal Neovascularization pathology
Humans
Inflammation genetics
Inflammation immunology
Inflammation metabolism
Inflammation pathology
Lymphatic Vessels immunology
Lymphatic Vessels pathology
Macrophages immunology
Macrophages pathology
Mice
Mice, Knockout
Neovascularization, Pathologic genetics
Neovascularization, Pathologic immunology
Neovascularization, Pathologic pathology
Thrombospondin 1 immunology
Thrombospondin 1 pharmacology
Vascular Endothelial Growth Factor C genetics
Vascular Endothelial Growth Factor C immunology
Vascular Endothelial Growth Factor C metabolism
CD36 Antigens metabolism
Lymphatic Vessels metabolism
Macrophages metabolism
Neovascularization, Pathologic metabolism
Thrombospondin 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 208
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21536744
- Full Text :
- https://doi.org/10.1084/jem.20092277