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Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes

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-o...

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Autores principales: Cursiefen, Claus, Maruyama, Kazuichi, Bock, Felix, Saban, Daniel, Sadrai, Zahra, Lawler, Jack, Dana, Reza, Masli, Sharmila
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092349/
https://www.ncbi.nlm.nih.gov/pubmed/21536744
http://dx.doi.org/10.1084/jem.20092277
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author Cursiefen, Claus
Maruyama, Kazuichi
Bock, Felix
Saban, Daniel
Sadrai, Zahra
Lawler, Jack
Dana, Reza
Masli, Sharmila
author_facet Cursiefen, Claus
Maruyama, Kazuichi
Bock, Felix
Saban, Daniel
Sadrai, Zahra
Lawler, Jack
Dana, Reza
Masli, Sharmila
author_sort Cursiefen, Claus
collection PubMed
description 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.
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spelling pubmed-30923492011-11-09 Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes Cursiefen, Claus Maruyama, Kazuichi Bock, Felix Saban, Daniel Sadrai, Zahra Lawler, Jack Dana, Reza Masli, Sharmila J Exp Med 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. The Rockefeller University Press 2011-05-09 /pmc/articles/PMC3092349/ /pubmed/21536744 http://dx.doi.org/10.1084/jem.20092277 Text en © 2011 Cursiefen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Cursiefen, Claus
Maruyama, Kazuichi
Bock, Felix
Saban, Daniel
Sadrai, Zahra
Lawler, Jack
Dana, Reza
Masli, Sharmila
Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title_full Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title_fullStr Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title_full_unstemmed Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title_short Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes
title_sort thrombospondin 1 inhibits inflammatory lymphangiogenesis by cd36 ligation on monocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092349/
https://www.ncbi.nlm.nih.gov/pubmed/21536744
http://dx.doi.org/10.1084/jem.20092277
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