title: Angiogenic Role of MMP-2/9 Expressed on the Cell Surface of Early Endothelial Progenitor Cells/Myeloid Angiogenic Cells.
abstract: Since the introduction of angiogenic cell therapy using early endothelial progenitor cells (EPCs), myeloid angiogenic cells (MACs) have been expected to be useful in treating ischemic diseases. In order to elucidate the angiogenic properties of MACs/EPCs, we clarified the characteristics of MACs as compared to M2 macrophages (Mϕs). Comparison of the gene expression profiles of MACs and late EPCs revealed that MACs expressed greater amounts of metalloproteinase (MMP)-9. It should be noted that the profile of MMP-2/9 expression on the cell surface of MACs was similar to that of M2 Mϕs, and that cell surface MMP-2/9 might be an active form based on molecular size. In addition, the invasion of MACs was prohibited not only by MMP-2/9 inhibitor, but also by the hyaluronidase treatment that caused the down-regulation of MMP-9 on the cell surface of MACs and inhibited their invasion activity. These results indicate that cell surface MMP-2/9 plays an important role in the high invasion ability of MACs. The conditioned medium of both MACs and M2 Mϕs stimulated tube formation of endothelial cells in vitro. MACs caused an increase in vessel formation in in vivo models through the production of IL-8. We propose that the role of MACs with cell surfaces expressing MMP-2/9 is rapidly invading ischemic tissue.
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagayaku, Tokyo, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Kanayasu-Toyoda
authors.affiliation: Nihon Pharmaceutical University, Komuro 10281, Inamachi, Kitaadachigun, Saitama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagayaku, Tokyo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii-Watabe
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagayaku, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: National Institute of Biomedical Innovation, 7-6-8 Asagi Saito Ibaraki-City, Osaka, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
authors.affiliation: Division of Cellular Gene Therapy Products, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Uchida
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagayaku, Tokyo, Japan.
authors.forename: Teruhide
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D017077:Culture Media, Conditioned; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8; D061965:Matrix Metalloproteinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9