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Related Experiment Videos

Proangiogenic function of CD40 ligand-CD40 interactions.

Marlies E J Reinders1, Masayuki Sho, Stuart W Robertson

  • 1Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|July 23, 2003
PubMed
Summary
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CD40 ligand (CD40L) promotes inflammation and angiogenesis by stimulating vascular endothelial growth factor (VEGF) production. This study demonstrates CD40L

Area of Science:

  • Immunology
  • Cell Biology
  • Vascular Biology

Background:

  • Angiogenesis is integral to immune-mediated inflammation.
  • The immunologic mediators of angiogenesis factor production remain largely unknown.
  • CD40 ligand (CD40L) interactions with CD40 influence inflammatory processes and vascular endothelial growth factor (VEGF) production by endothelial cells.

Purpose of the Study:

  • To investigate the role of CD40L in mediating angiogenesis.
  • To determine if CD40 ligation induces the expression of proangiogenic factors.
  • To assess the in vivo proangiogenic effects of CD40L.

Main Methods:

  • Cultured human endothelial cells were treated with anti-CD40 antibody to ligate CD40.
  • Human skin grafts on SCID mice were injected with saline, untransfected murine fibroblasts, or CD40L-transfected murine fibroblasts.

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  • Angiogenesis was assessed, and the expression of angiogenesis factors and VEGF was measured.
  • The effect of anti-VEGF treatment on CD40L-induced angiogenesis was evaluated.
  • Main Results:

    • CD40 ligation in vitro induced the expression of angiogenesis factors, including fibroblast growth factor-2, Flt-1, and Flt-4.
    • In vivo, injection of CD40L-expressing cells into human skin grafts induced significant angiogenesis and expression of VEGF and fibroblast growth factor.
    • Anti-VEGF treatment blocked the angiogenesis response to CD40L-expressing cells, indicating VEGF dependence.

    Conclusions:

    • CD40 ligation is a significant mediator of angiogenesis and inflammation at peripheral sites.
    • CD40L plays a critical role in promoting angiogenesis in vivo, dependent on VEGF.
    • These findings highlight the pathophysiological importance of CD40 signaling in inflammatory angiogenesis.