Abstract. Pogrammed cell death of peripheral blood mononuclear leucocytes from patients with acute inflammatory diseases (non-nosocomial pneumonia, acute appendicitis) was investigated under ex vivo conditions, upon cultivation of the cells with selective inhibitors of JNK (SP600125) and р38 МАРК (ML3403). In vitro addition of SP600125 and ML3403 under oxidative stress conditions prevents increase of annexinpositive mononuclear cells numbers, thus suggesting JNK and р38 МАР-kinases to be involved into oxidative mechanisms of apoptosis deregulation. A role of JNK in IL-8 production by mononuclear leucocytes was revealed in cases of acute inflammation. Regulatory effect of JNK and p38 MAP-kinases can be mediated through activation of redox-sensitive apoptogenic signal transduction systems, as well as due to changes in cellular cytokine-producing function.

Abstract. A study was performed aiming to investigate interactions between TNFα receptor (TNF1) superfamily and heat shock protein Hsp90, using a Jurkat tumor cell line. The tumor cells cultured in presence of Hsp90 inhibitor (17-AAG) showed increased numbers of cells, presenting surface TNFR1 and FasR, which facilitate triggering of programmed cell death. It was also revealed that Hsp90 blockage under the in vitro conditions causes a decrease in FasL, while not affecting TNFα and sTNFR1 production by the tumor cells. (Med. Immunol., 2011, vol. 13, N 2-3, pp 247-252)

Cytokine secretion, apoptosis and production of active oxygen forms in cell cultures for their in vitro contact with implants carrying microarc, magnetron or ablation calcium-phosphate coatings have been studied in the work. Mononuclear blood leukocytes have been established to be first of all cells regulating the acceptance/rejection of implants with different roughness. Implants with “smooth” calcium-phosphate coatings are less suitable for bone tissue reparative regeneration.

Hemopoietic islets, associations of stromal (macrophages, fibroblasts) and blood (including stem) cells, are structural and functional units of the bone marrow. We studied cellular and molecular processes developing following short-term (1 h) contact of hemopoietic islets with ferromagnetic nanoparticles in a multicellular system of the bone marrow in vitro. It was established that nanodispersions of magnetite (Fe(3)O(4), mean particle diameter 18 nm) and iron coated with carbon (Fe(C), particle diameter 5-10 nm) in a dose of 3 mg/liter had a minor effect on processes of necrotic and apoptotic cell death. Nanodispersion of carbon-coated iron (Fe(C)) most mildly stimulated oxidizing processes recorded by intracellular levels of reactive oxygen species. These nanoparticles, in contrast to magnetite, did not reduce the amount of hemopoietic islets in the bone marrow cell suspension.

We studied the in vitro apoptosis-inducing effect of recombinant TNF-α (rTNF-α) on blood lymphocytes from healthy donors. rTNF-α-induced apoptosis was accompanied by an increase in the number of cells with low mitochondrial transmembrane potential, increased intracellular content of reactive oxygen species, reduced content of Bcl-2, Bcl-xL, and Bax proteins, and elevated Bad content. The molecular mechanisms of these changes are discussed.

The effect of recombinant TNF-α on programmed death of donor lymphocytes was studied in vitro. The proapoptotic effect of this cytokine is realized through transcription factors and cell cycle inhibitors. Incubation of lymphocytes with recombinant TNF-α revealed increased levels of NF-kB and p21 and reducted content of nonphosphorylated p53.

The experimental-industrial technology of synthesizing nanostructured graphite by graphite fluoration by iodine heptafluoride and thermal decomposition of fluorinated graphite intercalated compounds has been developed. The experimental process installation was developed, the test batches of nano-structured graphite with high area of specific surface and adsorption capacity were produced; they were tested as a sorbing agent in bandaging medical materials.

The effects of recombinant IL-2 on apoptosis of lymphocytes of healthy donors were studied in in vitro experiments. It was shown that the inductive and inhibitory effects of IL-2 on apoptotic process depend on the dose of the cytokine and cell microenvironmental conditions. Culturing of lymphocytes with recombinant IL-2 increases the percent of cells with reduced transmembrane potential, reduces the content of intracellular proteins Bcl-2, Bcl-X L и Bax, and increases the level of Bad. The proapoptotic effect of this cytokine is realized with participation of nuclear transcription factor NF-кB and transcription factor P53.

In 76 patients with hepatitis C and tick-borne encephalitis revealed deficiency of T-cellular immunity. This defect is caused by disorders in lymphocyte apoptosis. Annexin test showed reduced apoptosis in patients with chronic viral hepatitis C and increased numbers of apoptotic lymphocytes in patients with tick-borne encephalitis. Differentiated evaluation of CD4(+) and CD8(+) lymphocyte apoptosis showed that long persistence of hepatitis C virus leads to increase of T-helper sensitivity to apoptosis induction. In patients with tick-borne encephalitis suppression of CD4(+) cell apoptosis realization was observed. Inhibition of CD8(+) lymphocyte apoptosis was detected also in patients with tick-borne encephalitis.

The cytogenetic status and activity of regulatory systems for stability of the cell genome were evaluated in patients with chronic viral persistence. Hepatitis B and C viruses damage the chromosome apparatus of peripheral blood lymphocytes. Cytogenetic instability of immunocompetent cells during chronic viral infection was associated with inhibition of DNA excision repair system and dysregulation of apoptosis in target cells.

The review summarizes information from recent literature and results of the authors' own investigations concerning dysbalance of programmed cell death in establishment of a long-term virus persistense. The article discusses molecular mechanisms of apoptosis modulation of immune cellls by persistent viruses.