title: Divergent effects of GM-CSF and TGFbeta1 on bone marrow-derived macrophage arginase-1 activity, MCP-1 expression, and matrix metalloproteinase-12: a potential role during arteriogenesis.
abstract: Granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor (TGF)beta1 induce arteriogenesis in a nonischemic model of femoral artery ligation. Moreover, clinical trials demonstrated an improved collateralization after injection of bone marrow cells. In the present study, the expression of arteriogenic factors in bone marrow-derived macrophages (BMDM) was measured to verify the potential of these cells to influence collateral artery growth. GM-CSF induced in BMDM the expression of monocyte chemoattractive protein (MCP)-1, matrix-metalloproteinase (MMP)-12, and arginase-1-the latter also showing a remarkable increase in activity. During in vivo induced arteriogenesis, the accumulation rate of macrophages around proliferating collaterals was significantly increased. We also show that MCP-1 is found to be mainly expressed in the media of the vessel wall, MMP-12 in macrophages of the adventitia, and arginase at both locations. This study provides for the first time a comprehensive analysis of GM-CSF/TGFbeta1-regulated arteriogenic factors in BMDM and supports the hypothesis that arteriogenesis is a multistage mechanism, including monocyte/macrophage adhesion and transmigration, pro-arteriogenic cytokine expression, degradation of connective tissue, and collagen synthesis regulation. Selective modulation of these mechanisms as well as cell-based therapies supplying arteriogenic factors in vivo point toward new strategies to influence collateral artery growth.
authors.affiliation: Research Group for Experimental and Clinical Arteriogenesis at the Department for Internal Medicine III, Albert-Ludwigs University Freiburg, Germany.
authors.forename: Marco M
authors.initials: MM
authors.lastname: Jost
authors.forename: Elena
authors.initials: E
authors.lastname: Ninci
authors.forename: Benjamin
authors.initials: B
authors.lastname: Meder
authors.forename: Caroline
authors.initials: C
authors.lastname: Kempf
authors.forename: Niels
authors.initials: N
authors.lastname: Van Royen
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
authors.forename: Bernhard
authors.initials: B
authors.lastname: Berger
authors.forename: Imo
authors.initials: I
authors.lastname: Hoefer
authors.forename: Manuel
authors.initials: M
authors.lastname: Modolell
authors.forename: Ivo
authors.initials: I
authors.lastname: Buschmann
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism / Q000502:physiology; D001158:Arteries / Q000254:growth & development*; D001854:Bone Marrow Cells / Q000502:physiology*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D013234:Stem Cells / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
chemical_list: D018932:Chemokine CCL2; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12; D001119:Arginase