Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor.
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.
Nakano
Keiji
K
First Department of Pathology, Kansai Medical University, 10-15 Moriguchi, Osaka, Japan.
Adachi
Yasushi
Y
Minamino
Keizo
K
Iwasaki
Masayoshi
M
Shigematsu
Akio
A
Kiriyama
Naoko
N
Suzuki
Yasuhiro
Y
Koike
Yasushi
Y
Mukaide
Hiromi
H
Taniuchi
Shoichiro
S
Kobayashi
Yohnosuke
Y
Kaneko
Kazunari
K
Ikehara
Susumu
S
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
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor