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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2011
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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. |
format | Text |
id | pubmed-3092349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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