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

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Cell Technologies in Biology and Medicine,  No. 3,  November,  2020

Microvesicles Produced by Natural Killer Cells Regulate the Formation of Blood Vessels K. L. Markova, A. R. Kozyreva, D. I. Sokolov, and S. A. Selkov

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 3, pp. 164-169, September, 2020 Original article submitted June 18, 2020 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. Key Words: angiogenesis; natural killers (NK) cells; microvesicles; endothelial cells Organs and tissues cannot function properly without oxygen and nutrient supply and without excretion of metabolic waste products. These processes are realized through extensive vascular network. In adults, vasculature is formed and developed through angiogenesis, a process during which new blood vessels are formed from pre-existing ones [10,26]. Angiogenesis is the key to renewal, regeneration, and branching of blood vessels. In adults, angiogenesis occurs during ovarian cycle and placentation, in the process of wound healing, or in the course of pathological processes, such as chronic inflammation or neoplasia. Angiogenesis can also be initiated in response to hypoxia, ischemia, or mechanical or physical damage [17]. By now, mechanisms and stages of angiogenesis have been studied sufficiently [5]. At the same time, regulation of angiogenesis remains one of the most popular areas in modern science, because it might provide opportunity for the treatment of pathologies resulting from inappropriate vascular development. Regulation of angiogenesis is affected by microenvironment of D. O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, St. Petersburg, Russia. Address for correspondence: [email protected]. K. L. Markova

endothelial cells (EC) due to their contact and distant interactions [15]. The distant effect is implemented via secretion of proangiogenic and antiangiogenic factors, including cytokines and growth factors, on the balanced production of which each stage of angiogenesis depends. Apart from cytokine secretion, the production of extracellular vesicles by both endothelial and microenvironment cells can also be a distant mechanism of angiogenesis regulation. It was shown that extracellular vesicles releas