UDC

612.112:[576.54+57.053.4]

DOI

10.37482/2542-1298-Z006

Authors

Marina Yu. Skorkina* ORCID: 0000-0002-9441-5295
Evgeniya A. Sladkova* ORCID: 0000-0003-3072-2402
Nina I. Zhernakova* ORCID: 0000-0001-7648-0774
Mikhail Yu. Pal’chikov* ORCID: 0000-0002-2426-1307
*Belgorod State National Research University (Belgorod, Russian Federation)
Corresponding author: Marina Skorkina, address: ul. Pobedy 85, Belgorod, 308015, Russian Federation; e-mail: skorkina@bsu.edu.ru

Abstract

Functional properties of biomembranes such as stiffness, charge, and adhesion largely determine the immunoregulatory activity of the granulocyte population. This paper aimed to investigate the functional (mechanical, adhesive and electrical) properties of granulocyte biomembranes in healthy people and patients with acute lymphoblastic leukaemia using a mechanical stress model in vitro. As a natural model of neoplastic process we chose acute lymphoblastic leukaemia, which involves dysfunction of the lymphoid link of the adaptive immune system and circulation of blasts. Using the mechanical stress model, the paper studied the effect produced by the elements of the purinergic signalling system on the functional properties of granulocyte biomembranes. Under the influence of mechanical stress, adenosine triphosphate (ATP) concentrations increased by the factor of 2.3 in healthy subjects and by the factor of 1.8 in patients with leukaemia, as compared with intact samples. At mechanical deformation of blood cells, in the group of healthy subjects the surface stiffness and charge decreased by 16.8 % (p < 0.05) and 47 % (p < 0.05) respectively, as compared with intact samples. In patients with acute lymphoblastic leukaemia, the surface stiffness decreased by 54.4 % (p < 0.05) while the adhesive force between erythrocyte and leukocyte increased by 30.7 % (p < 0.05) as compared with intact samples. Thus, the obtained data allow us to consider the ATP molecule as a paracrine regulatory element of intercellular signalling. Our findings can be used in the physiology of microcirculation to study the mechanisms of intercellular interaction in health and in developing leukaemia.
For citation: Skorkina M.Yu., Sladkova E.A., Zhernakova N.I., Pal’chikov M.Yu. Changes in the Functional Properties of Granulocyte Biomembranes in Health and in Patients with Acute Lymphoblastic Leukaemia at Mechanical Stress Modelling (in vitro). Journal of Medical and Biological Research, 2020, vol. 8, no. 2, pp. 157–165. DOI: 10.37482/2542-1298-Z006

Keywords

granulocytes, mechanical stress, functional properties of biomembranes, atomic force microscopy, acute lymphoblastic leukaemia

References

1. Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types? Front. Physiol., 2018, vol. 9. Art. no. 113.
2. Jablonska J., Lang S., Sionov R.V., Granot Z. The Regulation of Pre-Metastatic Niche Formation by Neutrophils. Oncotarget, 2017, vol. 8, no. 67, pp. 112132–112144.
3. Eruslanov E.B., Bhojnagarwala P.S., Quatromoni J.G., Stephen T.L., Ranganathan A., Deshpande C., Akimova T., Vachani A., Litzky L., Hancock W.W., Conejo-Garcia J.R., Feldman M., Albelda S.M., Singhal S. Tumor-Associated Neutrophils Stimulate T Cell Responses in Early-Stage Human Lung Cancer. J. Clin. Invest., 2014, vol. 124, no. 12, pp. 5466–5480.
4. Potter N.S., Harding C.V. Neutrophils Process Exogenous Bacteria via an Alternate Class I MHC Processing Pathway for Presentation of Peptides to T Lymphocytes. J. Immunol., 2001, vol. 167, no. 5, pp. 2538–2546.
5. Mishalian I., Bayuh R., Eruslanov E., Michaeli J., Levy L., Zolotarov L., Singhal S., Albelda S.M., Granot Z., Fridlender Z.G. Neutrophils Recruit Regulatory T-Cells into Tumors via Secretion of CLL 17 – a New Mechanism of Impaired Antitumor Immunity. Int. J. Cancer, 2014, vol. 135, no. 5, pp. 1178–1186.
6. North R.A. P2X Receptors. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 2016, vol. 371, no. 10700. Art. no. 20150427.
7. Di Virgilio F. P2X Receptors and Inflammation. Curr. Med. Chem., 2015, vol. 22, no. 7, pp. 866–877.
8. Di Virgilio F., Vuerich M. Purinergic Signaling in the Immune System. Auton. Neurosci., 2015, vol. 191, pp. 117–123.
9. Giannuzzo A., Pedersen S.F., Novak I. The P2X7 Receptor Regulates Cell Survival, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells. Mol. Cancer, 2015, vol. 14. Art. no. 203.
10. Lam W.A., Rosenbluth M.J., Fletcher D.A. Chemotherapy Exposure Increases Leukemia Cell Stiffness. Blood, 2007, vol. 109, no. 8, pp. 3505–3508.
11. Oonishi T., Sakashita K., Uyesaka N. Regulation of Red Blood Cell Filterability by Ca2+ Influx and cAMPMediated Signaling Pathways. Am. J. Physiol., 1997, vol. 273, no. 6, pp. C1828–C1834.
12. Trautmann A. Extracellular ATP in the Immune System: More Than Just a “Danger Signal”. Sci. Signal., 2009, vol. 2, no. 56, p. E6.
13. Fedorova M.Z., Zabinyakov N.A., Sladkova E.A. Sposob opredeleniya uprugosti kletok krovi [Method for Determining Blood Cell Elasticity]. Patent RF no. 2466401, 2011.
14. Skorkina M.Yu., Fedorova M.Z., Murav’ev A.V., Sladkova E.A. Ispol’zovanie nanomekhanicheskogo sensora dlya izucheniya morfofunktsional’nykh svoystv limfotsitov zdorovykh donorov i bol’nykh khronicheskim limfoblastnym leykozom [The Use of a Nanomechanical Sensor to Study the Morphofunctional Properties of Lymphocytes from Healthy Donors and Patients with Chronic Lymphocytic Leukemia]. Kletochnye tekhnologii v biologii i meditsine, 2012, no. 3, pp. 172–175.
15. Sladkova E.A., Skorkina M.Yu. Estimation of Surface Potential of Lymphocytes from Patients with Leukemia Using Kelvin Probe Mode. Biophysics, 2014, vol. 59, no. 2, pp. 254–256.
16. Skorkina M.Yu., Shamray E.A., Sladkova E.A. Izmerenie sil adgezii v sisteme “kletka–kletka” na osnove tekhnologiy atomno-silovoy mikroskopii [Measuring of Adhesion Force in the Cell–Cell System Based on Atomic Force Microscopy Technology]. Kletochnye tekhnologii v biologii i meditsine, 2017, no. 4, pp. 213–215.
17. Mittal D., Gubin M.M., Schreiber R.D., Smyth M.J. New Insights into Cancer Immunoediting and Its Three Component Phases – Elimination, Equilibrium and Escape. Curr. Opin. Immunol., 2014, vol. 27, pp. 16–25.
18. Goldman N., Chandler-Militello D., Lamgevin H.M., Nedergaard M., Takano T. Purine Receptor Mediated Actin Cytoskeleton Remodeling of Human Fibroblasts. Cell Calcium, 2013, vol. 53, no. 4, pp. 297–301.
19. Chen Y., Corriden R., Inoue Y., Yip L., Hashiguchi N., Zinkernagel A., Nizet V., Insel P.A., Junger W.G. ATP Release Guides Neutrophil Chemotaxis via P2Y2 and A3 Receptors. Science, 2006, vol. 314, no. 5806, pp. 1792–1795.
20. Olearczyk J.J., Ellsworth M.L., Stephenson A.H., Lonigro A.J., Sprague R.S. Nitric Oxide Inhibits ATP Release from Erythrocytes. J. Pharmacol. Exp. Ther., 2004, vol. 309, no. 3, pp. 1079–1084.
21. Sistigu A., Yamazaki T., Vacchelli E., Chaba K., Enot D.P., Adam J., Vitale I., Goubar A., Baracco E.E., Remédios C., et al. Cancer Cell-Autonomous Contribution of Type I Interferon Signaling to the Efficacy of Chemotherapy. Nat. Med., 2014, vol. 20, no. 11, pp. 1301–1309.
22. Montalbetti N., Leal Denis M.F., Pignataro O.P., Kobatake E., Lazarowski E.R., Schwarzbaum P.J. Homeostasis of Extracellular ATP in Human Erythrocytes. J. Biol. Chem., 2011, vol. 286, no. 44, pp. 38397–38407.
23. Egan T.M., Khakh B.S. Contribution of Calcium Ions to P2X Channel Responses. J. Neurosci., 2004, vol. 24, no. 13, pp. 3413–3420.
24. Abbott R.D., Koptiuch C., Iatridis J.C., Howe A.K., Badger G.J., Langevin H.M. Stress and Matrix-Responsive Cytoskeletal Remodeling in Fibroblasts. J. Cell Physiol., 2013, vol. 228, no. 1, pp. 50–57.
25. Migliorini C., Qian Y., Chen H., Brown E.B., Jain R.K., Munn L.L. Red Blood Cells Augment Leukocyte Rolling in a Virtual Blood Vessel. Biophys. J., 2002, vol. 83, no. 4, pp. 1834–1841.