RESUMO
BACKGROUND: During implantation, apoptosis is critical for the appropriate tissue remodeling of the maternal decidua and invasion of the developing embryo, yet the regulation of apoptosis is also imperative for a successful pregnancy. The quick and effective removal of apoptotic cells by tissue macrophages represents an essential process, which prevents the release of self-antigens, and in the case of pregnancy, paternal alloantigens. METHODS OF STUDY: Recent studies have shown that the process of apoptotic cell clearance is not a neutral event, but rather an active one that induces macrophage production of anti-inflammatory cytokines and survival factors. Apoptotic cell clearance is, therefore, necessary for the resolution of inflammatory conditions, which during pregnancy could have lethal consequences. CONCLUSIONS: The function of the maternal immune system during implantation and throughout pregnancy is, therefore, an important area of investigation. This review will discuss the role of decidual macrophages in apoptotic cell clearance during pregnancy.
Assuntos
Apoptose/fisiologia , Macrófagos/fisiologia , Fagocitose/fisiologia , Gravidez/fisiologia , Caspase 3 , Caspases/fisiologia , Citocinas/fisiologia , Decídua/citologia , Decídua/fisiologia , Implantação do Embrião/fisiologia , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Humanos , Leucócitos/fisiologia , Macrófagos/imunologia , Modelos Imunológicos , Fagocitose/imunologia , Placenta/citologia , Placenta/fisiologia , Placenta/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Gravidez/imunologia , Complicações na Gravidez/fisiopatologia , Proteínas/fisiologia , Trofoblastos/imunologia , Trofoblastos/fisiologia , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo XRESUMO
The Fas/Fas ligand (FasL) system has been suggested to play an important role in the establishment of an immune privilege status of the tumor by inducing Fas-mediated apoptosis in tumor-specific lymphocytes. However, the role of cell surface-expressed FasL in tumor cell protection has recently become controversial. In this study, we have demonstrated that ascites-derived epithelial ovarian cancer cells lack membranal FasL but constitutively secrete whole, intracellular FasL (37 kDa) via the release of microvesicles. In contrast, normal ovarian surface epithelial cells express, but do not secrete, FasL. We have also identified a heavily glycosylated form of secreted FasL (48 kDa), associated with microvesicles isolated directly from the ascites fluid of patients with ovarian cancer. Following the disruption of the microvesicle membrane, both the 37-kDa and 48-kDa forms of secreted FasL were able to trigger Fas-mediated apoptosis in Jurkat T cells. These results suggest that the release of secreted FasL, and not the membrane form, may provide a mechanism by which tumors might counterattack Fas-bearing immune cells, thus facilitating their escape from immune surveillance and promoting tumor cell survival.
