Department of Immunology and Intercellular Interactions, Federal State Budgetary Scientific Institution, Research Institute of Obstetrics, Gynecology, and Reproductology Named after D.O. Ott, 199034 St. Petersburg, Russia.
State Research Institute of Highly Pure Biopreparations, 197110 St. Petersburg, Russia.
Int J Mol Sci. 2021 Dec 20;22(24):13663. doi: 10.3390/ijms222413663.
Microvesicles (MVs) are plasma extracellular vesicles ranging from 100 (150) to 1000 nm in diameter. These are generally produced by different cells through their vital activity and are a source of various protein and non-protein molecules. It is assumed that MVs can mediate intercellular communication and modulate cell functions. The interaction between natural killer cells (NK cells) and endothelial cells underlies multiple pathological conditions. The ability of MVs derived from NK cells to influence the functional state of endothelial cells in inflammatory conditions has yet to be studied well. In this regard, we aimed to study the effects of MVs derived from NK cells of the NK-92 cell line stimulated with IL-1β on the phenotype, caspase activity, proliferation and migration of endothelial cells of the EA.hy926 cell line. Endothelial cells were cultured with MVs derived from cells of the NK-92 cell line after their stimulation with IL-1β. Using flow cytometry, we evaluated changes in the expression of endothelial cell surface molecules and endothelial cell death. We evaluated the effect of MVs derived from stimulated NK cells on the proliferative and migratory activity of endothelial cells, as well as the activation of caspase-3 and caspase-9 therein. It was established that the incubation of endothelial cells with MVs derived from cells of the NK-92 cell line stimulated with IL-1β and with MVs derived from unstimulated NK cells, leads to the decrease in the proliferative activity of endothelial cells, appearance of the pan leukocyte marker CD45 on them, caspase-3 activation and partial endothelial cell death, and reduced CD105 expression. However, compared with MVs derived from unstimulated NK cells, a more pronounced effect of MVs derived from cells of the NK-92 cell line stimulated with IL-1β was found in relation to the decrease in the endothelial cell migratory activity and the intensity of the CD54 molecule expression on them. The functional activity of MVs is therefore mediated by the conditions they are produced under, as well as their internal contents.
微泡 (MVs) 是直径在 100（150）至 1000nm 之间的血浆细胞外囊泡。这些通常是由不同的细胞通过其生命活动产生的，是各种蛋白质和非蛋白质分子的来源。据认为，MVs 可以介导细胞间通讯并调节细胞功能。自然杀伤细胞 (NK 细胞) 和内皮细胞之间的相互作用是多种病理状况的基础。NK 细胞来源的 MVs 影响炎症条件下内皮细胞功能状态的能力尚未得到很好的研究。在这方面，我们旨在研究 IL-1β 刺激的 NK-92 细胞系来源的 MV 对 EA.hy926 细胞系内皮细胞表型、半胱天冬酶活性、增殖和迁移的影响。内皮细胞用 IL-1β 刺激的 NK-92 细胞系细胞来源的 MV 培养。通过流式细胞术，我们评估了内皮细胞表面分子的表达和内皮细胞死亡的变化。我们评估了刺激 NK 细胞来源的 MV 对内皮细胞增殖和迁移活性的影响，以及其中 caspase-3 和 caspase-9 的激活。结果表明，与未刺激的 NK 细胞来源的 MV 相比，用 IL-1β 刺激的 NK-92 细胞系来源的 MV 孵育内皮细胞，导致内皮细胞增殖活性降低，其上出现泛白细胞标记物 CD45，caspase-3 激活和部分内皮细胞死亡，并降低 CD105 的表达。然而，与未刺激的 NK 细胞来源的 MV 相比，用 IL-1β 刺激的 NK-92 细胞系来源的 MV 孵育内皮细胞，发现内皮细胞迁移活性降低，其上 CD54 分子表达强度增强。MV 的功能活性因此受其产生条件及其内部内容物的调节。
