Медицинская иммунология (Jul 2022)
Phenotypic and functional characteristics of endothelial cells: the <i>in vitro</i> effects of protein fractions from the lysate of natural killer-derived microvesicles
Abstract
Microvesicles are membrane-derived formations ranging in size from 100 to 1000 nm, being produced by a variety of resting and activated cells. They can transfer their cargo to target cells, regulate physiological processes, and participate in the development of clinical disorders. Among the microvesicles of different origin, natural killers are of special interest. They represent a subpopulation of lymphocytes that eliminate aberrant cells, including virally infected and malignant cells, and participate in regulation of angiogenesis. By producing various stimuli and inhibitors of the latter process, natural killers are able to change functional activity of endothelial cells by means of microvesicle-mediated contacts. There are only scarce literature data on ability of the extracellular vesicles to influence endothelial functions, depending on the intrinsic balance of pro- and anti-angiogenic factors. Therefore, the aim of our study was to evaluate the effect of protein fractions derived from microvesicle lysate of the NK-92 natural killer cell line upon phenotype and functional characteristics of EA.hy926 endothelial cell line under in vitro experimental conditions. Using chromatographic micro-preparatory separation, twelve protein fractions (inducers) were obtained from the lysate. It was found that proliferation and migration of EA.hy926 cells after their cultivation with 10 of 12 protein fractions, were changed in different directions. These effects were dose-dependent, or remained unchanged, at distinct concentrations of active components in the fractions. The inducing factors from these fractions exerted predominantly stimulating effects on proliferation of the target cells, thus suggesting presence of proteins which are able of regulating endothelial functions. However, the size of residual area free of migrating endothelial cells treated by the inducers did not always correlate with the migration intensity and did not inversely correlate with the number of migrating cells. Moreover, it was found that the obtained protein fractions had no effect upon expression of CD54 (ICAM-1), CD34, CD31 (PECAM-1) and CD119 (IFNγR1) receptors by EA.hy926 cells. The data obtained confirm an involvement of microvesicles in communications between natural killer cells and endothelial cells, and presume different participation modes of microvesicle-derived effector proteins in the angiogenesis machinery.
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