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- Title
Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.
- Authors
Cursiefen, Claus; Maruyama, Kazuichi; Bock, Felix; Saban, Daniel; Sadrai, Zahra; Lawler, Jack; Dana, Reza; Masli, Sharmila
- 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.
- Publication
The Journal of experimental medicine, 2011, Vol 208, Issue 5, p1083
- ISSN
1540-9538
- Publication type
Journal Article
- DOI
10.1084/jem.20092277