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

57 Citations (Scopus)

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

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Monocytes
Endothelial Cells
Macrophages
Up-Regulation
Down-Regulation
CD31 Antigens
pleiotrophin
Chorioallantoic Membrane
Injections
Quail
von Willebrand Factor
Hindlimb
Fibrin
Nitric Oxide Synthase
Blood Vessels
Real-Time Polymerase Chain Reaction
Chickens
Embryonic Structures
Perfusion
Fluorescence

Keywords

  • Endothelial cell
  • Macrophage
  • Pleiotrophin
  • Transdifferentiation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells. / Sharifi, Behrooz G.; Zeng, Zhaohui; Wang, Lai; Song, Lei; Chen, Haiming; Qin, Minghui; Sierra-Honigmann, M. Rocio; Wachsmann-Hogiu, Sebastian; Shah, Prediman K.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 26, No. 6, 06.2006, p. 1273-1280.

Research output: Contribution to journalArticle

Sharifi, Behrooz G. ; Zeng, Zhaohui ; Wang, Lai ; Song, Lei ; Chen, Haiming ; Qin, Minghui ; Sierra-Honigmann, M. Rocio ; Wachsmann-Hogiu, Sebastian ; Shah, Prediman K. / Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2006 ; Vol. 26, No. 6. pp. 1273-1280.
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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.",
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T1 - Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells

AU - Sharifi, Behrooz G.

AU - Zeng, Zhaohui

AU - Wang, Lai

AU - Song, Lei

AU - Chen, Haiming

AU - Qin, Minghui

AU - Sierra-Honigmann, M. Rocio

AU - Wachsmann-Hogiu, Sebastian

AU - Shah, Prediman K.

PY - 2006/6

Y1 - 2006/6

N2 - 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.

AB - 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.

KW - Endothelial cell

KW - Macrophage

KW - Pleiotrophin

KW - Transdifferentiation

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