engleski

INTERPLAY OF PERFORIN AND GRANULYSIN AT THE MATERNAL-FETAL INTERFACE

Introduction. NK cells and cytotoxic T lymphocytes, main effectors in cell-mediated cytotoxicity, are heavily equipped with cytotoxic granules containing Perforin (PER), Granulysin (GNLY) and Granzymes. PER exerts its action by direct lysis of target cells and/or forming pores to allow GNLY to enter the target cell and initiate apoptosis. Previously we have found PER at the maternal-fetal interface in the quantities higher than in any other physiological or pathological conditions (Rukavina, D. Podack, E.R. Immunology Today 21:160-163, 2000). GNLY kills procariotic cells directly by interfering with cell membrane, but killing of eukariotic cells requires PER. Aim of the study. We investigated: 1) Expression of GNLY at the maternal-fetal interface in the first trimester of pregnancy and 2) the dynamics of changes in colocalization of PER and GNLY in the granules of decidual lymphocytes during their action. Results. The percentage of GNLY+ cells (~65%) in the decidual lymphocytes (DL) is much higher than in PBL (25%). All DL subpopulations abundantly express GNLY, especially NK cells (90%). dNK cells cultured for two hours in the medium only secrete high quantities of GNLY, higher than PBNK cells even following eighteen hours of cultivation. The level of GNLY mRNA expression in dNK cells is the highest compared to other cytolitic molecules including the PER. Colocalization analyses by confocal microscopy showed strong differences in GNLY and PER colocalization in the same granules. In DL only 10% of GNLY is localized in the same granules with the PER, significantly different to PBL (~60%). Similar relationships were found for PER. Following two hours cocultivation of DL with NK sensitive K-562 cell line the profile of GNLY and PER distribution in granules became similar to the profile in PBL. Conclusion. At the maternal-fetal interface GNLY and PER serve as a weapon of cytotoxic cells in the control of trophoblast invasion and defense against microbes, transformed or parasitized cells.

perforin; granulysin; maternal-fetal interface

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