Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Cursiefen, C; Maruyama, K; Bock, F; Saban, D; Sadrai, Z; Lawler, J; Dana, R; Masli, S
Published Date
- May 9, 2011
Published In
Volume / Issue
- 208 / 5
Start / End Page
- 1083 - 1092
PubMed ID
- 21536744
Pubmed Central ID
- PMC3092349
Electronic International Standard Serial Number (EISSN)
- 1540-9538
Digital Object Identifier (DOI)
- 10.1084/jem.20092277
Language
- eng
Conference Location
- United States