A112: Vascular endothelial growth factor (VEGF) modulates functional activity of murine peritoneal macrophages in vitro

Abstract

Recruitment of mononuclear phagocytes from the blood into tissues is considered to be a crucial process during inflammatory reactions, wound healing and tumor growth. Macrophages are known to reveal high plasticity and may change under the influence of microenvironment. The aim of the study was to evaluate the changes of macrophage functional activity under the influence of Vascular endothelial growth factor (VEGF) in vitro. This factor is known to be the main angiogenic factor but also possesses several immunomodulatory properties. Here we report that VEGF revealed a dose-dependent effects on cultured freshly isolated murine resident peritoneal macrophages: modulated iNOS mRNA expression, nitroxide and superoxide anion production, decreased 5′-nucleotidase (5′-N) activity, but had no influence on fluid-phase pinocytosis. Moreover, VEGF increased expression of its own mRNA via autocrine pathway as well as of VEGF protein expression. VEGF also induced up-regulation of extracellular matrix protein thrombospondin-1 (TSP-1) mRNA, which is considered as a part of macrophage activation phenotype. Production of cytokines and chemokines by macrophages was screened with the help of Multi- analyte ELISArray kits. It was found that incubation of macrophages in the presence of VEGF increased the production of angiogenic cytokines – TNF-α and IL-6 as well as several monocyte and leukocyte chemoattractants such as MCP-1, RANTES and MIP-1β. Therefore, we suggest that locally established VEGF gradient may influence inflammatory phenotype of tissue macrophages as well as potentiate their pro-angiogenic properties. This work was supported by Russian Foundation for Basic Research – Russia, Grant No. 15-04-06150 .