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Sharifi, B.G. et al.

Sharifi, Zeng, Wang, Song, Chen, Qin, Sierra-Honigmann, Wachsmann-Hogiu, Shah,

Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells.

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.[1]

References

Pleiotrophin induces transdifferentiation of monocytes into functional endothelial cells. Sharifi, B.G., Zeng, Z., Wang, L., Song, L., Chen, H., Qin, M., Sierra-Honigmann, M.R., Wachsmann-Hogiu, S., Shah, P.K. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]

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