title: Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor.
abstract: Recently we reported that macrophage colony-stimulating factor (M-CSF) can mobilize endothelial progenitor cells (EPCs) from the bone marrow into the peripheral blood, resulting in an increase in the number of blood vessels and augmentation of blood flow in the ischemia-induced legs. M-CSF accelerates neovascularization of ischemic lesions resulting from the mobilization of EPCs. In the present paper, we analyze the mechanisms underling the mobilization of EPCs by M-CSF. M-CSF augments the production of vascular endothelial growth factor (VEGF) from the bone marrow cells, especially from myeloid lineage cells. In vivo administration of anti-VEGF antibody abrogates both the acceleration of the recovery of blood flow in the ischemia-induced limbs by M-CSF and the augmentation of the mobilization of EPCs induced by M-CSF. These results suggest that the M-CSF contributes to rapid recovery of blood flow in ischemic lesions by mobilization of EPCs from the bone marrow through augmentation of VEGF production in the bone marrow and that the VEGF is mainly produced by myeloid lineage cells.
authors.affiliation: First Department of Pathology, Kansai Medical University, 10-15 Moriguchi, Osaka, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Nakano
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Adachi
authors.forename: Keizo
authors.initials: K
authors.lastname: Minamino
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Akio
authors.initials: A
authors.lastname: Shigematsu
authors.forename: Naoko
authors.initials: N
authors.lastname: Kiriyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Koike
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mukaide
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Taniuchi
authors.forename: Yohnosuke
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply* / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor