engleski

Human first trimester decidual macrophages display phenotypic and functional characteristics of alternative activation

INTRODUCTION: Immunocompetent cells in human first trimester decidua, predominantly maternal derived decidual NK cells and macrophages are in a close vicinity with a fetus originating invading extravillous cytotrophoblast cells but during normal pregnancy do not induce detrimental immune response. One of the possible reasons for this tolerance is enhancement of Th2 environment in placenta. Alternatively activated macrophages induced by IL-4, glucocorticoids, IL-10 or IL-13 display an immunosuppressive effect mediated by IL-10 and prostaglandin E2, downregulating Th1 and stimulating Th2 response. MS-1, coagulation factor XIIIa, fibronectin, IL-10, AMAC-1, prostaglandin E2, IL-1R-antagonist are considered as markers of alternatively activated macrophages. We investigate the hypothesis that classical activation of decidua macrophages leads to pregnancy termination by supporting Th1 immune response and that alternative activation favors pregnancy by supporting Th2 environment. AIM: In this study we examined phenothypic and functional characteristics of human first trimester decidual macrophages in order to establish whether they fit the pattern of alternative activation. MATERIAL AND METHODS: First trimester decidua tissues were obtained by elective pregnancy terminations. Tissues were either snap frozen, cryocut sectioned and acetone-fixed for immunohistology studies, or digested by enzymes to obtain single cell suspensions for flow cytometry analyses. Cell suspensions were either cultivated overnight with or without LPS and/or PMA for detection of presence and secretion of IL-10, or immediately labeled after isolation for detection of MS-1, fibronectin and factor XIIIa. RESULTS: Immunohistology confirmed presence of MS-1 in decidual tissue. Double immunofluorescence labeling of the tissue sections analyzed by laser scanning microscopy showed colocalization of MS-1 and CD14. Flow cytometric analyses of freshly isolated decidual cells confirmed colocalization of MS-1 and CD14, fibronectin and CD 14 and factor XIIIa and CD14. By the same technique, we confirmed the co expression of IL-10 and CD14 in cultivated decidual cells. Secretion of IL-10 by decidual macrophages was showed using flow cytometry secretion assay. CONCLUSION: Because decidual macrophages are expressing characteristics of alternative activation, our data suggest that these cells could be alternatively activated and in that way support Th2 environment in decidua favoring pregnancy over abortion. These investigations are supported by grant from Ministry of Science and Technology, Republic of Croatia and research in Graz was supported in part by grants from the provincial government of Styria and from the Franz-Lanyar-Stiftung to P.S. K.C. was supported by a grant from the Alps-Adria Association.

Decidual macrophages; Pregnancy; Alternative activation

nije evidentirano