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PMID: 16735597 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

G-CSF and AMD3100 mobilize monocytes into the blood that stimulate angiogenesis in vivo through a paracrine mechanism.

Blood ·Vol. 108 ·No. 7 ·2006-10-01 ·Pages 2438-45

Capoccia BJ, Shepherd RM, Link DC

Abstract

There is compelling evidence that circulating angiogenic cells exist that are able to home to sites of vascular injury and stimulate angiogenesis. However, the number of angiogenic cells in the blood is low, limiting their delivery to sites of ischemia. Treatment with certain cytokines may mobilize angiogenic cells into the blood, potentially circumventing this limitation. Herein, we show that treatment with granulocyte colony-stimulating factor (G-CSF) or AMD3100, a novel CXCR4 antagonist, significantly stimulated angiogenesis in a murine model of acute hindlimb ischemia. The kinetics of angiogenic-cell mobilization by these agents appears to be distinct, with more rapid revascularization observed in AMD3100-treated mice. Combination treatment with G-CSF and AMD3100 resulted in the earliest and most complete recovery in blood flow to the ischemic hindlimb. Adoptive transfer of mobilized blood mononuclear cells, while potently stimulating angiogenesis, did not result in the significant incorporation of donor cells into the neoendothelium. Cell-fractionation studies showed that it is the monocyte population in the blood that mediates angiogenesis in this model. Collectively, these data suggest that monocytes mobilized into the blood by G-CSF or AMD3100 stimulate angiogenesis at sites of ischemia through a paracrine mechanism.

MeSH Terms
Angiogenesis Inducing Agents/pharmacology Animals Benzylamines CD11b Antigen/biosynthesis Cyclams Cytokines/metabolism Granulocyte Colony-Stimulating Factor/metabolism Heterocyclic Compounds/metabolism Humans Mice Mice, Inbred C57BL Monocytes/cytology Neovascularization, Pathologic Paracrine Communication Receptors, CXCR4/metabolism
Chemicals
Angiogenesis Inducing Agents Benzylamines CD11b Antigen Cyclams Cytokines Heterocyclic Compounds Receptors, CXCR4 Granulocyte Colony-Stimulating Factor plerixafor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Capoccia Benjamin J
Division of Oncology, Washington University School of Medicine, Box 8007, 660 South Euclid Ave, St Louis, MO 63110, USA.
Shepherd Rebecca M
Link Daniel C
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-04-013755
Published
2006-10-01
Epub
2006-00-30
Pages
2438-45
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895560
Subset
IM
Grants
NCI NIH HHS · P30 CA91842 · United States
NHLBI NIH HHS · R01 HL 073762 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-04-013755 PMC Full Text View journal details
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