Каневский Леонид Михайлович

Избранные публикации

  1. Streltsova M.A., Klinkova A.V., Kuchukova A.A., Kadin A.Y., Kanevskiy L.M., Kovalenko E.I. (2016). Ethanol-dependent expression of the NKG2D ligands MICA/B in human cell lines and leukocytes. Biochem. Cell Biol. , 1–9 [+]

    Alcohol consumption affects the human immune system, causing a variety of disorders. However, the mechanisms of development of these changes are not fully understood. We hypothesized that ethanol may influence the expression of MICA and MICB, stress-induced molecules capable of regulating the activity of cytotoxic lymphocytes through the interaction with receptor NKG2D, which substantially affects the functionality of cellular immunity. We analyzed the effects of ethanol on MICA/B expression in tumor cell lines and human leukocytes. In the cell line models, ethanol caused different changes in the surface expression of MICA/B; in particular, it induced the translocation of intracellular proteins MICA/B to the cell surface and shedding of MICA (in soluble and microparticle-associated forms) from the plasma membrane. The observed results are not linked with cell death in cultures, taking place only under higher doses of ethanol. Ethanol at physiologically relevant concentrations (and higher) stimulated expression of MICA/B genes in different cell types. The effect of ethanol was more pronounced in hepatocyte line HepG2 compared with hematopoietic cell lines K562, Jurkat, and THP-1. Among the tested leukocytes, the most sensitive to ethanol action were T cells activated ex vivo with IL-2, in which the increase of MICA/B mRNA expression was registered with the smallest dose of ethanol (0.125%). In human monocytes, ethanol may lead to elevations in surface MICA/B levels. Presumably, changes in MICA/B expression caused by ethanol can affect the functions of NKG2D-positive cytotoxic lymphocytes, modulating immune reactions at excessive alcohol consumption.

  2. Клинкова А.В., Кузьмина Е.Г., Абакушина Е.В., Каневский Л.М., Неприна Г.С., Павлов В.В., Коваленко Е.И. (2016). Циркулирующий белок MICА у больных злокачественными лимфомами. Медицинская иммунология 18 (2), 151–162 ID:2030
  3. Kovalenko E.I., Boyko A.A., Semenkov V.F., Lutsenko G.V., Grechikhina M.V., Kanevskiy L.M., Azhikina T.L., Telford W.G., Sapozhnikov A.M. (2014). ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age. Oncotarget 5 (23), 11800–12 [+]

    ROS production and intracellular HSP70 levels were measured in human neutrophils for three age groups: young (20-59 years), elders (60-89 years) and nonagenarians (90 years and older). Elders showed higher levels of spontaneous intracellular ROS content compared with young and nonagenarian groups, which had similar intracellular ROS levels. Zymosan-induced (non-spontaneous) extracellular ROS levels were also similar for young and nonagenarians but were lower in elders. However, spontaneous extracellular ROS production increased continuously with age. Correlation analysis revealed positive relationships between HSP70 levels and zymosan-stimulated ROS production in the elder group. This was consistent with a promoting role for HSP70 in ROS-associated neutrophils response to pathogens. No positive correlation between ROS production and intracellular HSP70 levels was found for groups of young people and nonagenarians. In contrast, significant negative correlations of some ROS and HSP70 characteriscics were found for neutrophils from young people and nonagenarians. The observed difference in ROS and HSP70 correlations in elders and nonagenarians might be associated with an increased risk of mortality in older individuals less than 90 years old.

  4. Kanevskiy L.M., Erokhina S.A., Streltsova M.A., Telford W.G., Sapozhnikov A.M., Kovalenko E.I. (2014). Bacterial lipopolysaccharide activates CD57-negative human NK cells. Biochemistry Mosc. 79 (12), 1339–48 [+]

    NK cells play an important regulatory role in sepsis by induction and augmentation of proinflammatory reactions in early stages of the septic process and by suppression of immune response in later stages of inflammation. The present work was aimed at the effect of bacterial lipopolysaccharide (LPS), the main pathogenic factor of sepsis development, on human NK cells ex vivo. We show that LPS activates immature CD57-negative NK cells, which typically constitute less than half of the normal NK cell population in human peripheral blood. Under conditions of NK cell stimulation with IL-2, addition of LPS provokes an increase in IFN-γ production. However, LPS both increased and inhibited NK cell cytotoxic activity. It is important to note that the activation of NK cells on LPS addition was observed in the absence of TLR4 on the NK cell surface. These results confirm our previous data arguing for a direct interaction of LPS with NK cells and evidence an atypical mechanism of LPS-induced NK cell activation without the involvement of surface TLR4.

  5. Kanevskiy L.M., Telford W.G., Sapozhnikov A.M., Kovalenko E.I. (2013). Lipopolysaccharide induces IFN-γ production in human NK cells. Front Immunol 4, 11 [+]

    Natural killer (NK) cells have been shown to play a regulatory role in sepsis. According to the current view, NK cells become activated via macrophages or dendritic cells primed by lipopolysaccharide (LPS). Recently, TLR4 gene expression was detected in human NK cells suggesting the possibility of a direct action of LPS on NK cells. In this study, effects of LPS on NK cell cytokine production and cytotoxicity were studied using highly purified human NK cells. LPS was shown to induce IFN-γ production in the presence of IL-2 in NK cell populations containing>98% CD56(+) cells. Surprisingly, in the same experiments LPS decreased NK cell degranulation. No significant expression of markers related to blood dendritic cells, monocytes or T or B lymphocytes in the NK cell preparations was observed; the portions of HLA-DR(-bright), CD14(+), CD3(+), and CD20(+) cells amounted to less than 0.1% within the cell populations. No more than 0.2% of NK cells were shown to be slightly positive for surface TLR4 in our experimental system, although intracellular staining revealed moderate amounts of TLR4 inside the NK cell population. These cells were negative for surface CD14, the receptor participating in LPS recognition by TLR4. Incubation of NK cells with IL-2 or/and LPS did not lead to an increase in TLR4 surface expression. TLR4(-)CD56(+) NK cells isolated by cell sorting secreted IFN-γ in response to LPS. Antibody to TLR4 did not block the LPS-induced increase in IFN-γ production. We have also shown that R(e)-form of LPS lacking outer core oligosaccharide and O-antigen induces less cytokine production in NK cells than full-length LPS. We speculate that the polysaccharide fragments of LPS molecule may take part in LPS-induced IFN-γ production by NK cells. Collectively our data suggest the existence of a mechanism of LPS direct action on NK cells distinct from established TLR4-mediated signaling.

  6. Kovalenko E., Kanevskiy L., Klinkova A., Kuchukova A., Streltsova M., Telford W., Sapozhnikov A. (2012). Stress-Induced Molecules in Regulation of NK Cell Activity. Chapter in a book “Cell Interaction” , 93–120 ID:1168
  7. Mashkina A.P., Tyulina O.V., Solovyova T.I., Kovalenko E.I., Kanevski L.M., Johnson P., Boldyrev A.A. (2009). The excitotoxic effect of NMDA on human lymphocyte immune function. Neurochem. Int. 51 (6-7), 356–60 [+]

    N-Methyl-d-aspartate (NMDA)-activated glutamate receptors are expressed in lymphocytes, but their roles have not yet been defined. We show that incubation of human peripheral blood lymphocytes with NMDA resulted in increased intracellular calcium and reactive oxygen species (ROS) levels through effects on NMDA-activated glutamate receptors. In terms of ROS production, T cells were most affected, followed by NK cells, whereas B cell ROS levels were not increased. In unstimulated T and NK cells, interferon-gamma (IFN-gamma) production was unaffected by NMDA, whereas interleukin-2 stimulation of IFN-gamma production was significantly suppressed by NMDA. Simultaneous incubation of the cells with NMDA and IL-2 resulted in a dramatic increase in the amount of cells expressing the NR1 subunit of the NMDA-activated receptors. We conclude that NMDA-activated glutamate receptor activation, accompanied by the changes in intracellular calcium and ROS levels, may be involved in the modification of immune functions of human T and NK cells.

  8. Власкин П.А., Каневский Л.М., Стрельникова Ю.И., Сапожников А.М., Коваленко Е.И. (2007). Активирующее действие белка теплового шока 70 кДа на НК-клетки человека. Иммунология 28 (2), 74–79 ID:1198
  9. Коваленко Е.И., Власкин П.А., Каневский Л.М., Стрельникова Ю.И., Сапожников А.М. (2006). Влияние белков теплового шока 70 кДа на продукцию γ-интерферона натуральными киллерами человека. ДАН 406 (1), 1–4 ID:1202