Human NK cells internalize recombinant major stress protein HSP70
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Published:2023-06-01
Issue:3
Volume:25
Page:447-452
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ISSN:2313-741X
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Container-title:Medical Immunology (Russia)
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language:
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Short-container-title:Med. immunol.
Author:
Shevchenko M. A.1ORCID, Garbuz D. G.2, Davletshin A. I.2, Boyko A. A.1, Evgen'ev M. B.2, Sapozhnikov A. M.1
Affiliation:
1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences 2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
Abstract
Heat shock proteins 70 kDa (HSP70) protect intracellular proteins from the damaging effects of stress factors of various natures. Moreover, HSP70 play an important role in the vital activity of cells under normal physiological conditions, performing chaperone functions. These functions are realized in the intracellular space; however, in some cases, these proteins are also found on the cell surface and in the extracellular environment. The causes and mechanisms of HSP70 translocation to the cell surface and secretion into the extracellular space have not yet been well understood, but such an unusual localization of HSP70 activates the immune system. The surface HSP70 and their extracellular pool stimulate the cytotoxic activity of NK cells. However, direct experimental evidence for the internalization of HSP70 molecules by NK cells has not yet been demonstrated. This paper presents the results of the interaction of the extracellular HSP70 pool with NK cells from the peripheral blood. The results demonstrated the confirmation of the internalization of exogenous HSP70 molecules by NK cells. To this end, fluorescently labeled recombinant stress-inducible human HSP70 were obtained. The electrophoretic data indicated the absence of protein degradation during the labeling process, the purity and stability of the modified protein. To assess the interaction of HSP70 with NK cells, the fluorescently labeled HSP70 was added to an in vitro culture of NK cells isolated by magnetic separation from the peripheral blood mononuclear fraction and analyzed by confocal microscopy. This analysis indicated that living NK cells internalize extracellular HSP70 with localization both in lysosomes and in phagosomes. Our experiments illustrated for the first time the process of penetration of the extracellular form of HSP70 into these cells. The results suggest that the activation of NK cells under the action of exogenous HSP70 could be associated with the internalization of these protein molecules.
Subject
Immunology,Immunology and Allergy
Reference15 articles.
1. Arispe N., Doh M., Simakova O., Kurganov B., de Maio A. Hsc70 and HSP70 interact with phosphatidylserine on the surface of PC12 cells resulting in a decrease of viability. FASEB J., 2004, Vol. 18, no. 14, pp. 1636-1345. 2. Evgen’ev M., Bobkova N., Krasnov G., Garbuz D., Funikov S., Kudryavtseva A., Kulikov A., Samokhin A., Maltsev A., Nesterova I. The Effect of Human HSP70 Administration on a Mouse Model of Alzheimer’s Disease Strongly Depends on Transgenicity and Age. J. Alzheimers Dis., 2019, Vol. 67, no. 4, pp.1391-1404. 3. Gurskiy Y.G., Garbuz D.G., Soshnikova N.V., Krasnov A.N., Deikin A., Lazarev V.F., Sverchinskyi D., Margulis B.A., Zatsepina O.G., Karpov V.L., Belzhelarskaya S.N., Feoktistova E., Georgieva S.G., Evgen’ev M.B. The development of modified human HSP70 (HSPA1A) and its production in the milk of transgenic mice. Cell Stress Chaperones, 2016, Vol. 21, no. 6, pp. 1055-1064. 4. Guzhova I., Kislyakova K., Moskaliova O., Fridlanskaya I., Tytell M., Cheetham M., Margulis B. In vitro studies show that HSP70 can be released by glia and that exogenous HSP70 can enhance neuronal stress tolerance. Brain Res,. 2001, Vol. 914, no. 1-2, pp. 66-73. 5. Guzhova I.V., Arnholdt A.C., Darieva Z.A., Kinev A.V., Lasunskaia E.B., Nilsson K., Bozhkov V.M., Voronin A.P., Margulis B.A. Effects of exogenous stress protein 70 on the functional properties of human promonocytes through binding to cell surface and internalization. Cell Stress Chaperones, 1998, Vol. 3, no. 1, pp. 67-77.
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