Skip to main content

Advertisement

SpringerLink
Log in

Mass-Spectrometric Analysis of Proteome of Microvesicles Produced by NK-92 Natural Killer Cells

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

Membrane extracellular microvesicles serve as carriers of a wide range of molecules, the most important among these are proteins, lipids, and nucleic acids. Cytotoxic proteins of natural killer cells play a key role in the realization of their cytolytic functions. An important stage in understanding of the distant communication of cells and mechanisms of its regulation is analysis of the proteome composition of microvesicles. We studied the proteomic composition of microvesicles produced by NK-92 natural killer cells. Granzyme A, a specific protein of cytotoxic cells, has been identified in the microvesicles by QTOF-mass spectrometry. It was shown that heat shock proteins, components of the ubiquitin—proteasome system, enzymes of protein biosynthesis and energy metabolism, nuclear and serum proteins, as well as cytoskeleton proteins are associated with the microvesicles.

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. Govorun VM, Ivanov VT. Proteomics and peptidomics in fundamental and applied medical studies. Rus. J. Bioorgan. Chem. 2011;37(2):176-190.

    Article  CAS  Google Scholar 

  2. Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, Kiessling R, Jörnvall H, Wigzell H, Gudmundsson GH. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96(9):3086-3093.

    PubMed  CAS  Google Scholar 

  3. Almughlliq FB, Koh YQ, Peiris HN, Vaswani K, McDougall S, Graham EM, Burke CR, Arachchige BJ, Reed S, Mitchell MD. Exosomes or microvesicles? Two kinds of extracellular vesicles with different routes to modify protozoan-host cell interaction. Theriogenology. 2018;114:173-179.

    Article  PubMed  CAS  Google Scholar 

  4. Baig S, Kothandaraman N, Manikandan J, Rong L, Ee KH, Hill J, Lai CW, Tan WY, Yeoh F, Kale A, Su LL, Biswas A, Vasoo S, Choolani M. Proteomic analysis of human placental syncytiotrophoblast microvesicles in preeclampsia. Clin. Proteomics. 2014;11(1):40. Doi: https://doi.org/10.1186/1559-0275-11-40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Burbano C, Rojas M, Vásquez G, Castaño D. Microparticles that form immune complexes as modulatory structures in autoimmune responses. Mediators Inflamm. 2015;2015. ID 267590. Doi: https://doi.org/10.1155/2015/267590.

  6. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014;30:255-289.

    Article  PubMed  CAS  Google Scholar 

  7. Garcia BA, Smalley DM, Cho H, Shabanowitz J, Ley K, Hunt D.F. The platelet microparticle proteome. J. Proteome Res. 2005;4(5):1516-1521.

    Article  PubMed  CAS  Google Scholar 

  8. Gong JH, Maki G, Klingemann HG. Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia. 1994;8(4):652-658.

    PubMed  CAS  Google Scholar 

  9. 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). ID 1294368. doi: https://doi.org/10.1080/20013078.2017.1294368.

  10. 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  PubMed  PubMed Central  CAS  Google Scholar 

  11. Ko YH, Park S, Jin H, Woo H, Lee H, Park C, Kim K. Granzyme B leakage-induced apoptosis is a crucial mechanism of cell death in nasal-type NK/T-cell lymphoma. Lab. Invest. 2007;87(3):241-250.

    Article  PubMed  CAS  Google Scholar 

  12. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Théry C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc. Natl Acad. Sci USA. 2016;113(8):E968-E977.

    Article  PubMed  CAS  Google Scholar 

  13. Krensky AM, Clayberger C. Biology and clinical relevance of granulysin. Tissue Antigens. 2009;73(3):193-198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789-804.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Lugini L, Cecchetti S, Huber V, Luciani F, Macchia G, Spadaro F, Paris L, Abalsamo L, Colone M, Molinari A, Podo F, Rivoltini L, Ramoni C, Fais S. Immune surveillance properties of human NK cell-derived exosomes. J. Immunol. 2012;189(6):2833-2842.

    Article  PubMed  CAS  Google Scholar 

  16. Ma D, Cao W, Kapur A, Felder M, Scarlett CO, Patankar MS, Li L. Differential expression of proteins in I and IL-2 stimulated primary human NK cells identified by global proteomic analysis. J. Proteomics. 2013;91:151-163.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Miguet L, Pacaud K, Felden C, Hugel B, Martinez MC, Freyssinet JM, Herbrecht R, Potier N, van Dorsselaer A, Mauvieux L. Proteomic analysis of malignant lymphocyte membrane microparticles using double ionization coverage optimization. Proteomics. 2006;6(1):153-171.

    Article  PubMed  CAS  Google Scholar 

  18. Nawrot R, Barylski J, Schulze WX. Incorrectly annotated keratin derived peptide sequences lead to misleading MS/MS data interpretation. J. Proteomics. 2013;91:270-273.

    Article  PubMed  CAS  Google Scholar 

  19. Scheiter M, Lau U, van Ham M, Bulitta B, Gröbe L, Garritsen H, Klawonn F, König S, Jänsch L. Proteome analysis of distinct developmental stages of human natural killer (NK) cells. Mol. Cell Proteomics. 2013;12(5):1099-1114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Screpanti V, Wallin RP, Grandien A, Ljunggren HG. Impact of FASL-induced apoptosis in the elimination of tumor cells by NK cells. Mol. Immunol. 2005;42(4):495-499.

    Article  PubMed  CAS  Google Scholar 

  21. Shoae-Hassani A, Hamidieh AA, Behfar M, Mohseni R, Mortazavi-Tabatabaei SA, Asgharzadeh S. NK cell-derived exosomes from NK cells previously exposed to neuroblastoma cells augment the antitumor activity of cytokine-activated NK cells. J. Immunother. 2017;40(7):265-276.

    Article  PubMed  CAS  Google Scholar 

  22. Sokolov DI, Ovchinnikova OM, Korenkov DA, Viknyanschuk AN, Benken KA, Onokhin KV, Selkov SA. Influence of peripheral blood microparticles of pregnant women with preeclampsia on the phenotype of monocytes. Transl. Res. 2016;170:112-123.

    Article  PubMed  CAS  Google Scholar 

  23. Taylor RN, Roberts JM, Cunningham FG, Lindheimer MD, Chesley LC. Chesley’s Hypertensive disorders in pregnancy. Amsterdam; Boston, 2015.

  24. Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 2009; 9(8):581-593.

    Article  PubMed  CAS  Google Scholar 

  25. Théry C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2002;2(8):569-579.

    Article  PubMed  CAS  Google Scholar 

  26. Thiery J, Keefe D, Boulant S, Boucrot E, Walch M, Martinvalet D, Goping IS, Bleackley RC, Kirchhausen T, Lieberman J. Perforin pores in the endosomal membrane trigger the release of endocytosed granzyme B into the cytosol of target cells. Nat. Immunol. 2011;12(8):770-777.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Tramontano AF, Lyubarova R, Tsiakos J, Palaia T, Deleon JR, Ragolia L. Circulating endothelial microparticles in diabetes mellitus. Mediators Inflamm. 2010;2010. ID 250476. Doi: https://doi.org/10.1155/2010/250476.

  28. 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  PubMed  Google Scholar 

  29. van Eden W, Jansen MAA, Ludwig I, van Kooten P, van der Zee R, Broere F. The enigma of heat shock proteins in immune tolerance. Front. Immunol. 2017;8:1599. doi: https://doi.org/10.3389/fimmu.2017.01599.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 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  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    A. V. Korenevskii, Yu. P. Milyutina, A. A. Zhdanova, K. M. Pyatygina, D. I. Sokolov & S. A. Sel’kov

Authors
  1. A. V. Korenevskii
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu. P. Milyutina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. A. Zhdanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. M. Pyatygina
    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 A. V. Korenevskii.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 108-116, June, 2018

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Korenevskii, A.V., Milyutina, Y.P., Zhdanova, A.A. et al. Mass-Spectrometric Analysis of Proteome of Microvesicles Produced by NK-92 Natural Killer Cells. Bull Exp Biol Med 165, 564–571 (2018). https://doi.org/10.1007/s10517-018-4214-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-018-4214-7

Key Words

Search

Navigation