Skip to main content
Log in

Microvesicles Produced by Natural Killer Cells Regulate the Formation of Blood Vessels

  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of microvesicles derived from cells of the NK-92 cell line on the formation of tube-like structures by endothelial cells of the ЕА.Hy926 cell line. Microvesicles were isolated by differential centrifugation and their size was controlled by granulometric analysis using dynamic light scattering method. The effect of microvesicles produced by NK cells on angiogenesis was evaluated by cultural methods. In the course of the research, a model of co-culturing of microvesicles and endothelial cells on extracellular matrix Matrigel was developed. It was found that microvesicles derived from NK-92 cells promoted elongation of tube-like structures formed by endothelial ЕА.Hy926 cells. Microvesicles produced by NK cells can modulate functional activity of endothelial cells by affecting their ability to form blood vessels.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abhinand CS, Raju R, Soumya SJ, Arya PS, Sudhakaran PR. VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis. J. Cell Commun. Signal. 2016;10(4):347-354.

    Article  Google Scholar 

  2. Aoki N, Yokoyama R, Asai N, Ohki M, Ohki Y, Kusubata K, Heissig B, Hattori K, Nakagawa Y, Matsuda T. Adipocytederived microvesicles are associated with multiple angiogenic factors and induce angiogenesis in vivo and in vitro. Endocrinology. 2010;151(6):2567-2576.

    Article  CAS  Google Scholar 

  3. Bauvois B. New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression. Biochim. Biophys. Acta. 2012;1825(1):29-36.

    CAS  PubMed  Google Scholar 

  4. Budaj M, Poljak Z, Ďuriš I, Kaško M, Imrich R, Kopáni M, Maruščáková L, Hulín I. Microparticles: a component of various diseases. Pol. Arch. Med. Wewn. 2012;122(Suppl 1):24-29.

    CAS  PubMed  Google Scholar 

  5. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011;473:298-307.

    Article  CAS  Google Scholar 

  6. Chen WS, Kitson RP, Goldfarb RH. Modulation of human NK cell lines by vascular endothelial growth factor and receptor VEGFR-1 (FLT-1). In Vivo. 2002;16(6):439-445.

    CAS  PubMed  Google Scholar 

  7. Edsparr K, Johansson BR, Goldfarb RH, Basse PH, Nann-mark U, Speetjens FM, Kuppen PJ, Lennernäs B, Albertsson P. Human NK cell lines migrate differentially in vitro related to matrix interaction and MMP expression. Immunol. Cell Biol. 2009;87(6):489-495.

    Article  CAS  Google Scholar 

  8. Jong AY, Wu CH, Li J, Sun J, Fabbri M, Wayne AS, Seeger RC. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells. J. Extracell. Vesicles. 2017;6(1):1294368. doi: https://doi.org/10.1080/20013078.2017.1294368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kalra H, Drummen GP, Mathivanan S. Focus on extracellular vesicles: introducing the next small big thing. Int. J. Mol. Sci. 2016;17(2):170. doi: https://doi.org/10.3390/ijms17020170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kholia S, Ranghino A, Garnieri P, Lopatina T, Deregibus MC, Rispoli P, Brizzi MF, Camussi G. Extracellular vesicles as new players in angiogenesis. Vascul. Pharmacol. 2016;86:64-70.

    Article  CAS  Google Scholar 

  11. Kim CW, Lee HM, Lee TH, Kang C, Kleinman HK, Gho YS. Extracellular membrane vesicles from tumor cells promote angiogenesis via sphingomyelin. Cancer Res. 2002;62(21):6312-6317.

    CAS  PubMed  Google Scholar 

  12. Kleinman HK, Martin GR. Matrigel: basement membrane matrix with biological activity. Semin. Cancer Biol. 2005;15(5):378-386.

    Article  CAS  Google Scholar 

  13. Leroyer AS, Rautou PE, Silvestre JS, Castier Y, Lesèche G, Devue C, Duriez M, Brandes RP, Lutgens E, Tedgui A, Boulanger CM. CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. J. Am. Coll. Cardiol. 2008;52(16):1302-1311.

    Article  CAS  Google Scholar 

  14. Li J, Zhang Y, Liu Y, Dai X, Li W, Cai X, Yin Y, Wang Q, Xue Y, Wang C, Li D, Hou D, Jiang X, Zhang J, Zen K, Chen X, Zhang CY. Microvesicle-mediated transfer of microRNA-150 from monocytes to endothelial cells promotes angiogenesis. J. Biol. Chem. 2013;288(32):23,586-23,596.

    Article  CAS  Google Scholar 

  15. Markova KL, Stepanova OI, Sheveleva AR, Kostin NA, Mikhailova VA, Selkov SA, Sokolov DI. Natural killer cell effects upon angiogenesis under conditions of contact-dependent and distant co-culturing with endothelial and trophoblast cells. Med. Immunol. (Rus). 2019;21(3):427-440.

    Article  Google Scholar 

  16. Mostefai HA, Andriantsitohaina R, Martínez MC. Plasma membrane microparticles in angiogenesis: role in ischemic diseases and in cancer. Physiol. Res. 2008;57(3):311-320.

    CAS  PubMed  Google Scholar 

  17. Papetti M, Herman IM. Mechanisms of normal and tumor- derived angiogenesis. Am. J. Physiol. Cell Physiol. 2002;282(5):C947-C970.

    Article  CAS  Google Scholar 

  18. Ponce ML. Tube formation: an in vitro matrigel angiogenesis assay. Methods Mol. Biol. 2009;467:183-188.

    Article  CAS  Google Scholar 

  19. Sadallah S, Eken C, Schifferli JA. Ectosomes as modulators of inflammation and immunity. Clin. Exp. Immunol. 2011;163(1):26-32.

    Article  CAS  Google Scholar 

  20. Sedgwick AE, D’Souza-Schorey C. The biology of extracellular microvesicles. Traffic. 2018;19(5):319-327.

    Article  CAS  Google Scholar 

  21. Simak J, Gelderman MP, Yu H, Wright V, Baird AE. Circulating endothelial microparticles in acute ischemic stroke: a link to severity, lesion volume and outcome. J. Thromb. Haemost. 2006;4(6):1296-1302.

    Article  CAS  Google Scholar 

  22. Sokolov DI, Markova KL, Mikhailova VA, Vyazmina LP, Milyutina YuP, Kozyreva AR, Zhdanova AA, Malygina DA, Onokhin KV, Ivanova AN, Korenevsky AV, Selkov SA. Phenotypic and functional characteristics of microvesicles produced by natural killer cells. Med. Immunol. (Russ). 2019;21(4):669-688.

    Article  Google Scholar 

  23. Soleti R, Martinez MC. Sonic Hedgehog on microparticles and neovascularization. Vitam. Horm. 2012;88:395-438.

    Article  CAS  Google Scholar 

  24. Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat- George F. Extracellular vesicles in angiogenesis. Circ. Res. 2017;120(10):1658-1673.

    Article  CAS  Google Scholar 

  25. Turu MM, Slevin M, Matou S, West D, Rodríguez C, Luque A, Grau-Olivares M, Badimon L, Martinez-Gonzalez J, Krupinski J. C-reactive protein exerts angiogenic effects on vascular endothelial cells and modulates associated signalling pathways and gene expression. BMC Cell Biol. 2008;9:47. doi: https://doi.org/10.1186/1471-2121-9-47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Udan RS, Culver JC, Dickinson ME. Understanding vascular development. Wiley Interdiscip. Rev. Dev. Biol. 2013;2(3):327-346.

  27. van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J. Thromb. Haemost. 2014;12(7):1182-1192.

    Article  Google Scholar 

  28. Yang C, Mwaikambo BR, Zhu T, Gagnon C, Lafleur J, Seshadri S, Lachapelle P, Lavoie J.C, Chemtob S, Hardy P. Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008;294(2):R467-R476.

    Article  CAS  Google Scholar 

  29. Zhu L, Kalimuthu S, Gangadaran P, Oh JM, Lee HW, Baek SH, Jeong SY, Lee SW, Lee J, Ahn BC. Exosomes derived from natural killer cells exert therapeutic effect in melanoma. Theranostics. 2017;7(10):2732-2745.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to K. L. Markova.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 164-169, September, 2020

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Markova, K.L., Kozyreva, A.R., Sokolov, D.I. et al. Microvesicles Produced by Natural Killer Cells Regulate the Formation of Blood Vessels. Bull Exp Biol Med 170, 123–127 (2020). https://doi.org/10.1007/s10517-020-05017-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-020-05017-y

Key Words

Navigation