Premium
Divergent effects of GM‐CSF and TGFβ 1 on bone marrow‐ derived macrophage arginase‐1 activity, MCP‐1 expression, and matrix‐metalloproteinase‐12: a potential role during arteriogenesis
Author(s) -
Jost Marco M.,
Ninci Elena,
Meder Benjamin,
Kempf Caroline,
Royen Niels van,
Hua Jing,
Berger Bernhard,
Hoefer Imo,
Modolell Manuel,
Buschmann Ivo
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0071fje
Subject(s) - arteriogenesis , arginase , monocyte , bone marrow , macrophage , cytokine , transforming growth factor , in vivo , matrix metalloproteinase , medicine , microbiology and biotechnology , immunology , cancer research , chemistry , endocrinology , biology , in vitro , biochemistry , angiogenesis , amino acid , arginine
Granulocyte/macrophage‐colony stimulating factor (GM‐CSF) and transforming growth factor (TGF)β 1 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/TGFβ 1‐ 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.