Macrophage-induced neovascularization in a murine model of acute inflammation induced by LPS increasing VEGF-A and MMP-9 expression.

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

Viña del Mar, Chile

Congreso; 9th Latin American Congress of Immunology; 2009

The role of macrophages (MP) in angiogenesis during septic shock (SS) is almost unknown. Here we investigate the production of inflammatory mediators by MP and its angiogenicity in a BALB/c model of SS induced by lypopolysaccharide (LPS). MP treated in vitro with LPS (10 ug/ml) produced higher levels of nitric oxide (NO) than untreated MP (p<0.05) concomitantly with an increase in nitric oxide synthase 2 expression by Western blot (Wb) (D.O.) (p<0.05) via NF-kB. We also observed an increment in metalloprotease-9 (MMP-9) activity induced by LPS vs. untreated MP (p<0.05). LPS also generated MP capable to induce neovascularization in vivo (Nº vessels/mm2 skin) (MP: 1.35±0.13; MP+LPS: 2.18±0.19; p<0.01). By Wb we demonstrated that LPS increased the expression of MMP-9 (control: 3.96±0.02; LPS: 6.60±0.05; p<0.05), CD-31 (control: 23.00±0.03; LPS: 28.00±0.11; p<0.05) and vascular endothelial growth factor-A (VEGF-A) (control: 0.90±0.07; LPS: 1.80±0.04; p<0.05) in the angiogenic skin. We observed that MP obtained from BALB/c mice treated in vivo with LPS (i.p.) (1 ug/g) up-regulated the expression of VEGF-A (p<0.05) and MMP-9 (p<0.05). In conclusion murine MP are able to respond to LPS increasing the production of inflammatory mediators as NO, MMP-9 and VEGF-A in vitro and also can induce neovascularization in vivo.