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

被引:120
作者
Capoccia, Benjamin J.
Shepherd, Rebecca M.
Link, Daniel C.
机构
[1] Washington Univ, Sch Med, Div Oncol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO 63110 USA
关键词
ENDOTHELIAL PROGENITOR CELLS; CYTOKINE-INDUCED MOBILIZATION; ACUTE HINDLIMB ISCHEMIA; GROWTH-FACTOR; HEMATOPOIETIC STEM; NEOVASCULARIZATION; EXPRESSION; RECEPTOR; TRANSPLANTATION; RECRUITMENT;
D O I
10.1182/blood-2006-04-013755
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 angio-genesis 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 angio-genesis, 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.
引用
收藏
页码:2438 / 2445
页数:8
相关论文
共 50 条
[1]   Mobilizing endothelial progenitor cells [J].
Aicher, A ;
Zeiher, AM ;
Dimmeler, S .
HYPERTENSION, 2005, 45 (03) :321-325
[2]   Monocyte activation in angiogenesis and collateral growth in the rabbit hindlimb [J].
Arras, M ;
Ito, WD ;
Scholz, D ;
Winkler, B ;
Schaper, J ;
Schaper, W .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (01) :40-50
[3]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[4]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[5]   PROLIFERATIVE AND MIGRATORY RESPONSES OF MURINE MICROVASCULAR ENDOTHELIAL-CELLS TO GRANULOCYTE-COLONY-STIMULATING FACTOR [J].
BOCCHIETTO, E ;
GUGLIELMETTI, A ;
SILVAGNO, F ;
TARABOLETTI, G ;
PESCARMONA, GP ;
MANTOVANI, A ;
BUSSOLINO, F .
JOURNAL OF CELLULAR PHYSIOLOGY, 1993, 155 (01) :89-95
[6]   Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist [J].
Broxmeyer, HE ;
Orschell, CM ;
Clapp, DW ;
Hangoc, G ;
Cooper, S ;
Plett, PA ;
Liles, WC ;
Li, XX ;
Graham-Evans, B ;
Campbell, TB ;
Calandra, G ;
Bridger, G ;
Dale, DC ;
Srour, EF .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (08) :1307-1318
[7]   Mechanisms of angiogenesis and arteriogenesis [J].
Carmeliet, P .
NATURE MEDICINE, 2000, 6 (04) :389-395
[8]  
Couffinhal T, 1998, AM J PATHOL, V152, P1667
[9]   Impaired collateral vessel development associated with reduced expression of vascular endothelial growth factor in ApoE-/- mice [J].
Couffinhal, T ;
Silver, M ;
Kearney, M ;
Sullivan, A ;
Witzenbichler, B ;
Magner, M ;
Annex, B ;
Peters, K ;
Isner, JM .
CIRCULATION, 1999, 99 (24) :3188-3198
[10]   Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation [J].
Crosby, JR ;
Kaminski, WE ;
Schatteman, G ;
Martin, PJ ;
Raines, EW ;
Seifert, RA ;
Bowen-Pope, DF .
CIRCULATION RESEARCH, 2000, 87 (09) :728-730