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Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts

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Abstract

Studies of interactions between natural killer (NK) cells and trophoblasts and identification of conditions for the NK cells to perform their cytotoxic function are of fundamental and practical importance for understanding their role in the development of pathological processes and complications during pregnancy. In this study, we examined changes in the content of caspases and studied activation of these enzymes in Jeg-3 trophoblasts in various models of their coculturing with NK-92 cells and demonstrated the necessity of direct contact between these cell populations for the activation of caspase-8 and caspase-3 in the trophoblasts. Contact coculturing of the two cell lines resulted in the appearance of the cytotoxic protein granzyme B in Jeg-3 cells that was accompanied by a decrease in the content of this enzyme in NK-92 cells. Distant coculturing of NK-92 and Jeg-3 cells did not trigger initiator and effector caspases characteristic for the apoptosis development in Jeg-3 cells. The observed decrease in the content of procaspases in the trophoblasts may be associated with alternative non-apoptotic functions of these enzymes.

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Abbreviations

CFSE:

5(6)-carboxyfluorescein diacetate N-succinimidyl ester

dNK cell:

decidual natural killer cell

FITC:

fluorescein isothiocyanate

IFN-γ:

interferon γ

pNK cell:

peripheral blood NK cell

TNF-α:

tumor necrosis factor α

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Funding

This work was supported by the Science School grant NSh_2873.2018.7 and State Budget Project no. AAAA_A19_119021290116_1.

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  1. Ott Institute of Obstetrics, Gynecology, and Reproductology, 199034, St. Petersburg, Russia

    Yu. P. Milyutina, V. A. Mikhailova, K. M. Pyatygina, E. S. Demidova, D. A. Malygina, T. E. Tertychnaia, A. V. Arutjunyan, D. I. Sokolov & S. A. Selkov

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  1. Yu. P. Milyutina
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Correspondence to Yu. P. Milyutina.

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Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 10, pp. 1460–1472.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-121, September 16, 2019.

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Milyutina, Y.P., Mikhailova, V.A., Pyatygina, K.M. et al. Role of Caspases in the Cytotoxicity of NK-92 Cells in Various Models of Coculturing with Trophoblasts. Biochemistry Moscow 84, 1186–1196 (2019). https://doi.org/10.1134/S0006297919100079

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