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Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.

Publication ,  Journal Article
Cursiefen, C; Maruyama, K; Bock, F; Saban, D; Sadrai, Z; Lawler, J; Dana, R; Masli, S
Published in: J Exp Med
May 9, 2011

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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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 9, 2011

Volume

208

Issue

5

Start / End Page

1083 / 1092

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor C
  • Thrombospondin 1
  • Neovascularization, Pathologic
  • Mice, Knockout
  • Mice
  • Macrophages
  • Lymphatic Vessels
  • Inflammation
  • Immunology
  • Humans
 

Citation

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Cursiefen, C., Maruyama, K., Bock, F., Saban, D., Sadrai, Z., Lawler, J., … Masli, S. (2011). Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med, 208(5), 1083–1092. https://doi.org/10.1084/jem.20092277
Cursiefen, Claus, Kazuichi Maruyama, Felix Bock, Daniel Saban, Zahra Sadrai, Jack Lawler, Reza Dana, and Sharmila Masli. “Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.J Exp Med 208, no. 5 (May 9, 2011): 1083–92. https://doi.org/10.1084/jem.20092277.
Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, et al. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med. 2011 May 9;208(5):1083–92.
Cursiefen, Claus, et al. “Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.J Exp Med, vol. 208, no. 5, May 2011, pp. 1083–92. Pubmed, doi:10.1084/jem.20092277.
Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, Dana R, Masli S. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med. 2011 May 9;208(5):1083–1092.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 9, 2011

Volume

208

Issue

5

Start / End Page

1083 / 1092

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factor C
  • Thrombospondin 1
  • Neovascularization, Pathologic
  • Mice, Knockout
  • Mice
  • Macrophages
  • Lymphatic Vessels
  • Inflammation
  • Immunology
  • Humans