title: Role of neutrophil-derived matrix metalloproteinase-9 in tissue regeneration.
abstract: Ischemic tissue regeneration depends on neovascularization, the growth of new blood vessels. Bone marrow (BM)-derived cells, including neutrophils, have been shown to contribute to neovascularization during hind limb ischemia and inflammation. Neutrophils produce a broad array of angiogenic growth factors and proteases, which promote remodeling of arterioles into arteries through proteolytic mechanisms. Matrix metalloproteinases (MMPs) have been shown to play a role in the recruitment of neutrophils to sites of inflammation, which requires the extravascular migration of neutrophils through the extracellular matrix. Neutrophils control critical steps during angiogenesis and neutrophil-derived MMPs can promote neoangiogenesis, and collateral growth and perfusion recovery, in part by liberating vital angiogenic growth factors, including vascular endothelial growth factor-A (VEGF-A). This review focuses on the role of neutrophils as key players in the control of the angiogenic process during ischemic tissue regeneration. Aspects of neutrophil regulation, in particular regulation by its major growth factor granulocyte colony-stimulating factor (G-CSF), the role of the unique, readily available, neutrophil-derived MMP-9, and the functional consequences of this MMP-9 activation for angiogenesis, such as MMP-mediated release of biologically relevant cytokines from the matrix and cell surfaces, will be discussed.
authors.affiliation: Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Beate
authors.initials: B
authors.lastname: Heissig
authors.forename: Chiemi
authors.initials: C
authors.lastname: Nishida
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tashiro
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishihara
authors.forename: Makiko
authors.initials: M
authors.lastname: Ohki
authors.forename: Ismael
authors.initials: I
authors.lastname: Gritli
authors.forename: Jeanette
authors.initials: J
authors.lastname: Rosenkvist
authors.forename: Koichi
authors.initials: K
authors.lastname: Hattori
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D007511:Ischemia / Q000201:enzymology* / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009504:Neutrophils / Q000201:enzymology*; D012038:Regeneration / Q000502:physiology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9