Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
MetadataShow full item record
CitationCursiefen, Claus, Kazuichi Maruyama, Felix Bock, Daniel Saban, Zahra Sadrai, Jack Lawler, Reza Dana, and Sharmila Masli. 2011. “Thrombospondin 1 Inhibits Inflammatory Lymphangiogenesis by CD36 Ligation on Monocytes.” The Journal of Experimental Medicine 208 (5) (May 2): 1083–1092. doi:10.1084/jem.20092277.
AbstractLymphangiogenesis 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34387114
- HMS Scholarly Articles