Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor

Keiji Nakano; Yasushi Adachi; Keizo Minamino; Masayoshi Iwasaki; Akio Shigematsu; Naoko Kiriyama; Yasuhiro Suzuki; Yasushi Koike; Hiromi Mukaide; Shoichiro Taniuchi; Yohnosuke Kobayashi; Kazunari Kaneko; Susumu Ikehara

doi:10.1634/stemcells.2005-0421

Mechanisms underlying acceleration of blood flow recovery in ischemic limbs by macrophage colony-stimulating factor

Stem Cells. 2006 May;24(5):1274-9. doi: 10.1634/stemcells.2005-0421. Epub 2006 Feb 2.

Authors

Keiji Nakano¹, Yasushi Adachi, Keizo Minamino, Masayoshi Iwasaki, Akio Shigematsu, Naoko Kiriyama, Yasuhiro Suzuki, Yasushi Koike, Hiromi Mukaide, Shoichiro Taniuchi, Yohnosuke Kobayashi, Kazunari Kaneko, Susumu Ikehara

Affiliation

¹ First Department of Pathology, Kansai Medical University, 10-15 Moriguchi, Osaka, Japan.

PMID: 16456135
DOI: 10.1634/stemcells.2005-0421

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Marrow Cells / chemistry
Cells, Cultured
Disease Models, Animal
Endothelial Cells / cytology*
Endothelial Cells / drug effects
Endothelial Cells / physiology
Endothelium, Vascular / cytology*
Endothelium, Vascular / drug effects
Endothelium, Vascular / physiology
Granulocyte Colony-Stimulating Factor / genetics
Granulocyte Colony-Stimulating Factor / pharmacology
Hindlimb / blood supply*
Hindlimb / physiopathology
Humans
Ischemia / drug therapy*
Ischemia / physiopathology
Macrophage Colony-Stimulating Factor / genetics
Macrophage Colony-Stimulating Factor / pharmacology
Macrophage Colony-Stimulating Factor / physiology*
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic*
Receptors, Granulocyte Colony-Stimulating Factor / analysis
Receptors, Granulocyte Colony-Stimulating Factor / metabolism
Recombinant Proteins / metabolism
Regional Blood Flow / drug effects

Substances

Receptors, Granulocyte Colony-Stimulating Factor
Recombinant Proteins
Granulocyte Colony-Stimulating Factor
Macrophage Colony-Stimulating Factor