Macrophages modulate neovascular response in an acute model of imflammation. Expression of pro-angiogenic proteins

DE LA TORRE, EULALIA; HOVSEPIAN, EUGENIA; GOREN, NORA; SALES, MARÍA ELENA

Buenos Aires

Congreso; First French-Argentine Immunology Congress; 2010

SAI

Macrophages modulate neovascular response in an acute model of imflammation. Expression of pro-angiogenic proteins   de la Torre, Eulalia; Hovsepian, Eugenia; Goren, Nora; Sales, María Elena. Centro de  Estudios Farmacológicos y Botánicos (CEFYBO)-CONICET, Facultad de Medicina, Universidad de Buenos Aires.   Septic shock (SS) induced by bacterial infections, affect mainly the cardiovascular system. This damage is caused by microorganisms themselves or their endotoxins, and may be enhanced by the infiltration of immune cells in the myocardium. The role of macrophages (MP) in inflammatory angiogenesis during SS is almost unknown. We investigated the angiogenic abitility of peritoneal MP in a model of acute inflammation induced by lippopolysaccharide (LPS) from E. coli in BALB/c mice. We demonstrated that MP are able to stimulate neovascularization at 5x105 per site, and treatment with LPS (10 ug/ml) in vitro (LPS-MP) reduces MP number required to produce angiogenesis (4x105) potentating this effect (number of skin vessels/mm2) (normal skin: 1.13 ± 0.20; MP: 1.35 ± 0.13; LPS-MP: 2.18 ± 0.19, p <0.01). Furthermore, by Western blot (Wb) (relative D.O.), we observed that LPS-MP also increase the expression of proangiogenic proteins at the site of inoculation: MMP-9 (MP: 0.36, LPS-MP: 0.64, p <0.05), CD-31 (MP: 0.73, LPS-MP: 1.01, p <0.05) and VEGF-A (MP: 0.13, LPS-MP: 0.73, p <0.05). In vitro, LPS-MP have increased activity of MMP-9 in comparison with MP without treatment (p <0.05) via nuclear factor kB (NF- kB). In addition we studied the role of MP obtained from BALB/c mice treated in vivo with LPS (1 ug/g; i.p.). We observed an up-regulation of MMP-9 (MP: not detected, LPS-MP: 1.01, p <0.05) and VEGF-A expression (MP: not detected; LPS-MP: 1.29, p <0.05) compared to MP from untreated animals. Normal hearts were cultured with MP or supernatants MP from BALB/c mice treated in vivo with LPS and homogenates showed an increment in proangiogenic molecules expression: CD31 and VEGF-A (p <0.05). We conclude that peritoneal MP are inducers of angiogenesis and infection with LPS enhances their proangiogenic effect. In addition, MP modulate the level of expression of angiogenic molecules in normal hearts and this action enable them as modulators of cardiac angiogenesis during the SS.