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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3198-3204.
Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-04-1485.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
PDGF-D induces macrophage recruitment, increased interstitial pressure, and blood vessel maturation during angiogenesis
Marko Uutela,
Maria Wirzenius,
Karri Paavonen,
Iiro Rajantie,
Yulong He,
Terhi Karpanen,
Marja Lohela,
Helge Wiig,
Petri Salven,
Katri Pajusola,
Ulf Eriksson, and
Kari Alitalo
From the Molecular/Cancer Biology Laboratory and the Ludwig Institute for Cancer Research, Haartman Institute and Helsinki University Hospital Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland; Department of Biomedicine, University of Bergen, Norway; and Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institute, Sweden.
Platelet-derived growth factor-D (PDGF-D) is a recently characterized member of the PDGF family with unknown in vivo functions. We investigated the effects of PDGF-D in transgenic mice by expressing it in basal epidermal cells and then analyzed skin histology, interstitial fluid pressure, and wound healing. When compared with control mice, PDGF-D transgenic mice displayed increased numbers of macrophages and elevated interstitial fluid pressure in the dermis. Wound healing in the transgenic mice was characterized by increased cell density and enhanced recruitment of macrophages. Macrophage recruitment was also the characteristic response when PDGF-D was expressed in skeletal muscle or ear by an adeno-associated virus vector. Combined expression of PDGF-D with vascular endothelial growth factor-E (VEGF-E) led to increased pericyte/smooth muscle cell coating of the VEGF-E–induced vessels and inhibition of the vascular leakiness that accompanies VEGF-E–induced angiogenesis. These results show that full-length PDGF-D is activated in tissues and is capable of increasing interstitial fluid pressure and macrophage recruitment and the maturation of blood vessels in angiogenic processes.
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