Cursiefen, ClausMaruyama, KazuichiBock, FelixSaban, DanielSadrai, ZahraLawler, JackDana, RezaMasli, Sharmila2017-11-272011Cursiefen, 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.20092277.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:34387114Lymphangiogenesis 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.en-USJournal Article2017-06-1920112017-11-2710.1084/jem.20092277