Phagocytosis and IFN-y mediated signalization in the materno-fetal interface

• Grant number: 02/09407-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2003
• End date: October 31, 2008
• Field of knowledge: Biological Sciences - Morphology
• Principal Investigator: Estela Maris Andrade Forell Bevilacqua
• Grantee: Estela Maris Andrade Forell Bevilacqua
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In many species, phagocytosis is a remarkable characteristic exhibited by implanting and post-implanting trophoblast cells. Particularly in mice, during the first half of the gestation, giant trophoblast cells phagocytose maternal endometrial cells and among them, blood cells, which may have a role in nutrition and acquisition of space for embryo development. Throughout gestation "however, phagocytosis of microorganisms can also be experimentally observed. In relation to the phagocytic activity, trophoblast cells and macrophages share several characteristics, such as reactive oxygen species production" C3b-mediated phagocytosis, production of nitric oxide, and both increase their potential for phagocytosis in the presence of IFN-y. In macrophages, IFN-y is a potent regulatory molecule for phagocytosis and able to suppress the synthesis of cytoplasmic proteins involved in viral replication, to active the transcription factor NF-KB involved in inflammatory defense response and to induce the production of oxide nitric and oxidases responsible for reactive oxygen species formation. On the other hand, IFN-y produced by immune and non-immune cells is present in the materno-fetal interface and is considered a physiological component of gestation. However, under conditions in which the immune/inflammatory response against pathogens prolongs non-physiological concentrations of IFN-y in the matemo organism, pregnancy may be affected. So, considering that phagocytosis is an inherent activity of trophoblast cells, which can be related to defense functions, this study aims to determine the concentrations of IFN-y in normal gestation and in pregnant remates challenged with LPS; to determine the maximum IFN-y concentration that does not interfere with the gestation progression; to establish in vivo and in vitro models that allow the study of the process of phagocytosis by trophoblast cells of microorganisms or part of them; to evaluate the action of IFN-y on the gene expression of trophoblast cells and mainly, on the expression of nitric oxide synthase, using DNA macroarray approaches. (AU)