Skip to main content
SpringerLink
Log in

Interaction of NK Cells, Trophoblast, and Endothelial Cells during Angiogenesis

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied changes in angiogenesis during contact interaction of natural killer cells and endothelial cells in the presence of secretory products of trophoblast cells activated by various cytokines. Activated trophoblast regulates angiogenesis by producing soluble factors that affect endothelial cells either directly or indirectly through activation of proangiogenic activity of natural killer cells. A stimulating effect of the trophoblast supernatants activated by IL-1β and an inhibitory effect of trophoblast supernatants activated by IL-6 and TGFβ for the formation of tube-like structures by endothelial cells were revealed. During contact culturing, natural killer cells increased the length of tube-like structures formed by endothelial cells. The trophoblast activated by IL-1β affects angiogenesis both directly through the production of proangiogenic factors and indirectly through activation of the proangiogenic potential of natural killer cells. Trophoblast activated by IFNγ affects angiogenesis only by stimulating the proangiogenic potential of natural killer cells. Under conditions of contact interaction of natural killer cells and endothelial cells, soluble factors of trophoblast activated by IL-6 or TGFβ attenuated the angiogenesis-stimulating effect of natural killer cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barbosa BF, Lopes-Maria JB, Gomes AO, Angeloni MB, Castro AS, Franco PS, Fermino ML, Roque-Barreira MC, Ietta F, Martins-Filho OA, Silva DA, Mineo JR, Ferro EA. IL10, TGF beta1, and IFN gamma modulate intracellular signaling pathways and cytokine production to control Toxoplasma gondii infection in BeWo trophoblast cells. Biol. Reprod. 2015;92(3):82. doi: https://doi.org/10.1095/biolreprod.114.124115.

    Article  CAS  PubMed  Google Scholar 

  2. Bills VL, Hamdollah-Zadeh M, Soothill PW, Harper SJ, Bates DO. The role of VEGF-A165b in trophoblast survival. BMC Pregnancy Childbirth. 2014;14:278. doi: https://doi.org/10.1186/1471-2393-14-278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Burton GJ, Jauniaux E. What is the placenta? Am. J. Obstet. Gynecol. 2015;213(4, Suppl. S6.e1), S6-8. doi: https://doi.org/10.1016/j.ajog.2015.07.050.

    Article  PubMed  Google Scholar 

  4. Cao G, Savani RC, Fehrenbach M, Lyons C, Zhang L, Coukos G, Delisser HM. Involvement of endothelial CD44 during in vivo angiogenesis. Am. J. Pathol. 2006;169(1):325-336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cerdeira AS, Rajakumar A, Royle CM, Lo A, Husain Z, Thadhani RI, Sukhatme VP, Karumanchi SA, Kopcow HD. Conversion of peripheral blood NK cells to a decidual NKlike phenotype by a cocktail of defined factors. J. Immunol. 2013;190(8):3939-3948.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cheng JC, Chang HM, Fang L, Sun YP, Leung PC. TGF-b1 up-regulates connexin43 expression: a potential mechanism for human trophoblast cell differentiation. J. Cell Physiol. 2015;230(7):1558-1566.

    Article  CAS  PubMed  Google Scholar 

  7. Cheng JC, Chang HM, Leung PCK. TGF-b1 inhibits human trophoblast cell invasion by upregulating connective tissue growth factor expression. Endocrinology. 2017;158(10):3620-3628.

    Article  PubMed  Google Scholar 

  8. Dallagi A, Girouard J, Hamelin-Morrissette J, Dadzie R, Laurent L, Vaillancourt C, Lafond J, Carrier C, Reyes-Moreno C. The activating effect of IFN-g on monocytes/macrophages is regulated by the LIF-trophoblast-IL-10 axis via Stat1 inhibition and Stat3 activation. Cell. Mol. Immunol. 2015;12(3):326-341.

    Article  CAS  PubMed  Google Scholar 

  9. El Omar R, Xiong Y, Dostert G, Louis H, Gentils M, Menu P, Stoltz JF, Velot É, Decot V. Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells. Immunol. Cell Biol. 2016;94(4):342-356.

    Article  CAS  PubMed  Google Scholar 

  10. Faas MM, de Vos P. Uterine NK cells and macrophages in pregnancy. Placenta. 2017;56:44-52.

    Article  CAS  PubMed  Google Scholar 

  11. Felker AM, Croy BA. Natural cytotoxicity receptor 1 in mouse uNK cell maturation and function. Mucosal Immunol. 2017;10(5):1122-1132.

    Article  CAS  PubMed  Google Scholar 

  12. Fons P, Chabot S, Cartwright JE, Lenfant F, L’Faqihi F, Giustiniani J, Herault JP, Gueguen G, Bono F, Savi P, Aguerre-Girr M, Fournel S, Malecaze F, Bensussan A, Plouët J, Le Bouteiller P. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood. 2006;108(8):2608-2615.

    Article  CAS  PubMed  Google Scholar 

  13. Forbes K, Westwood M. Maternal growth factor regulation of human placental development and fetal growth. J. Endocrinol. 2010;207(1):1-16.

    Article  CAS  PubMed  Google Scholar 

  14. Hofmann AP, Gerber SA, Croy BA. Uterine natural killer cells pace early development of mouse decidua basalis. Mol. Hum. Reprod. 2014;20(1):66-76.

    Article  CAS  PubMed  Google Scholar 

  15. Huang Z, Li S, Fan W, Ma Q. Transforming growth factor b1 promotes invasion of human JEG-3 trophoblast cells via TGFb/Smad3 signaling pathway. Oncotarget. 2017;8(20):33,560-33,570.

    Google Scholar 

  16. Kim M, Park HJ, Seol JW, Jang JY, Cho YS, Kim KR, Choi Y, Lydon JP, Demayo FJ, Shibuya M, Ferrara N, Sung HK, Nagy A, Alitalo K, Koh GY. VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodelling during pregnancy. EMBO Mol. Med. 2013;5(9):1415-1430.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lash GE, Schiessl B, Kirkley M, Innes BA, Cooper A, Searle RF, Robson SC, Bulmer JN. Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy. J. Leukoc. Biol. 2006;80(3):572-580.

    Article  CAS  PubMed  Google Scholar 

  18. Mikhailova VA, Belyakova KL, Selkov SA, Sokolov DI. Peculiarities of NK cells differentiation: CD56dim and CD56bright NK cells at pregnancy and in non-pregnant state. Med. Immunol (Russia). 2017;19(1):19-26. doi: https://doi.org/10.15789/1563-0625-2017-1-19-26.

    Article  Google Scholar 

  19. Nwabuobi C, Arlier S, Schatz F, Guzeloglu-Kayisli O, Lockwood CJ, Kayisli UA. hCG: biological functions and clinical applications. Int. J. Mol. Sci. 2017;18(10). pii: E2037. doi: https://doi.org/10.3390/ijms18102037.

  20. Park SY, Yun S, Ryu BJ, Han AR, Lee SK. Trophoblasts regulate natural killer cells via control of interleukin-15 receptor signaling. Am. J. Reprod. Immunol. 2017;78(2). doi: https://doi.org/10.1111/aji.12628.

  21. Pontillo A, Girardelli M, Agostinis C, Masat E, Bulla R, Crovella S. Bacterial LPS differently modulates inflammasome gene expression and IL-1b secretion in trophoblast cells, decidual stromal cells, and decidual endothelial cells. Reprod. Sci. 2013;20(5):563-566.

    Article  CAS  PubMed  Google Scholar 

  22. Robson A, Harris LK, Innes BA, Lash GE, Aljunaidy MM, Aplin JD, Baker PN, Robson SC, Bulmer JN. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB J. 2012;26(12):4876-4885.

    Article  CAS  PubMed  Google Scholar 

  23. Scaife PJ, Bulmer JN, Robson SC, Innes BA, Searle RF. Effector activity of decidual CD8+ T lymphocytes in early human pregnancy. Biol. Reprod. 2006;75(4):562-567.

    Article  CAS  PubMed  Google Scholar 

  24. Sharma S, Godbole G, Modi D. Decidual control of trophoblast invasion. Am. J. Reprod. Immunol. 2016;75(3):341-350.

    Article  CAS  PubMed  Google Scholar 

  25. Sokolov DI, Furaeva KN, Stepanova OI, Sel’kov SA. Proliferative and Migration Activity of JEG-3 Trophoblast Cell Line in the Presence of Cytokines. Bull. Exp. Biol. Med. 2015;159(4):550-556.

    Article  CAS  PubMed  Google Scholar 

  26. Southcombe J, Tannetta D, Redman C, Sargent I. The immunomodulatory role of syncytiotrophoblast microvesicles. PLoS One. 2011;6(5):e20245. doi: https://doi.org/10.1371/journal.pone.0020245.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Straszewski-Chavez SL, Abrahams VM, Mor G. The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr. Rev. 2005;26(7):877-897.

    Article  CAS  PubMed  Google Scholar 

  28. Wallace AE, Fraser R, Cartwright JE. Extravillous trophoblast and decidual natural killer cells: a remodelling partnership. Hum. Reprod. Update. 2012;18(4):458-471.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Walshe TE. TGF-beta and microvessel homeostasis. Microvasc. Res. 2010;80(1):166-173.

    Article  CAS  PubMed  Google Scholar 

  30. Zhang J, Dunk CE, Kwan M, Jones RL, Harris LK, Keating S, Lye SJ. Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy. Cell. Mol. Immunol. 2017;14(2):203-213.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. D. O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, Russia

    K. L. Belyakova, O. I. Stepanova, A. R. Sheveleva, V. A. Mikhailova, D. I. Sokolov & S. A. Sel’kov

Authors
  1. K. L. Belyakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. I. Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. R. Sheveleva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. A. Mikhailova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. I. Sokolov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. A. Sel’kov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. I. Sokolov.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 1, pp. 54-62, January, 2019

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Belyakova, K.L., Stepanova, O.I., Sheveleva, A.R. et al. Interaction of NK Cells, Trophoblast, and Endothelial Cells during Angiogenesis. Bull Exp Biol Med 167, 169–176 (2019). https://doi.org/10.1007/s10517-019-04484-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-019-04484-2

Key Words

Search

Navigation