Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells

Behrooz G. Sharifi, Zhaohui Zeng, Lai Wang, Lei Song, Haiming Chen, Minghui Qin, M. Rocio Sierra-Honigmann, Sebastian Wachsmann-Hogiu, Prediman K. Shah

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

OBJECTIVE - Pleiotrophin (PTN) is a cytokine that is expressed by monocytes/macrophages in ischemic tissues and that promotes neovascularization, presumably by stimulating proliferation of local endothelial cells. However, the effect of PTN on monocytes/macrophages remains unknown. We investigated the role of PTN in regulating the phenotype of monocytes/macrophages. METHODS AND RESULTS - RT-PCR, real-time PCR, and fluorescence-activated cell sorter analysis revealed that the expression of PTN by monocytic cells led to a downregulation of CD68, c-fms, and CD14 monocytic cell markers and an upregulation of FLK-1, Tie-2, vascular endothelial-cadherin, platelet endothelial cell adhesion molecule-1, endothelial NO synthase, von Willebrand factor, CD34, GATA-2, and GATA-3 endothelial cell markers. Fibrin gel assays showed that the treatment of mouse and human monocytic cells with PTN led to the formation of tube-like structures. In vivo studies showed that PTN-expressing monocytic cells incorporated into the blood vessels of the quail chorioallantoic membrane. The intracardial injection of PTN-expressing monocytic cells into chicken embryos showed that cells integrated only into the developing vasculature. Finally, the injection of PTN-expressing monocytes into a murine ischemic hindlimb model significantly improved perfusion of the ischemic tissue. CONCLUSIONS - PTN expression by monocytes/macrophages led to a downregulation of their monocytic cell markers and an upregulation of endothelial cell characteristics, thus inducing the transdifferentiation of monocytes into functional endothelial cells.

Original languageEnglish (US)
Pages (from-to)1273-1280
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • Endothelial cell
  • Macrophage
  • Pleiotrophin
  • Transdifferentiation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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