[Expression of integrins ß1, α4 and cell adhesion molecule ICAM-1 in the presence of sodium deoxyribonucleate with ferrum complex (DNA-Na-Fe) by MT-4 cells transformed by human T-lymphotropic virus type 1 (Retroviridae: Orthoretrovirinae: Deltaretrovirus: Human T-lymphotropic virus type 1)].

INTRODUCTION: The important role of integrins (IG) in the initiation and development of cancer processes makes these structures convenient targets for the development of immunomodulatory therapeutic drugs that have an effect directly on these molecules. Among the latter, IG ß1, α4 and cell adhesion receptor ICAM-1 (intercellular adhesion molecule 1) are of particular interest. Immunomodulators are capable of changing the IG activity through non-specific mechanisms, which, however, in some cases can cause a decrease in the protective functions of the immune system and health deterioration.The aim of the study was to determine the effect on the levels of cellular expression and the nature of IG metabolism of the drug sodium deoxyribonucleate with ferrum complex, DNA-Na-Fe, which is having been used in the Russian Federation as an immunomodulatory agent, but whose action has not been studied in details so far. MATERIAL AND METHODS: We used 2 variants of the neoplastic CD4+ T-lymphocyte cell line transformed with human T-lymphotropic virus type 1 (HTLV-1) of the Retroviridae family, MT-4 (MT-4/1 and MT-4/2). The indicated variants were characterized by different levels of expression of the protein activation markers CD28 and CD38. After cell culture in the presence of 500 µg/ml DNA-Na-Fe, the expression levels of IG ß1 (CD29), α4 (CD49d), and ICAM-1 (CD54) were studied by flow cytometry. RESULTS: The cells of the both lines contained many membrane proteins CD29+ (90.4% ± 4.5) and CD54+ (97.9% ± 1.4), while small percentage of cells contained protein CD49d+ (1.9% ± 1.0). No changes in the expression of the studied proteins were observed in the presence of the drug. DISCUSSION: The levels of IG ß1, α4 and ICAM-1 expression may serve as one of the phenotypic characteristics of MT-4 cells. The obtained data are of great importance because the peculiarities of CD4+ T-lymphocytes transformation and their metabolism during HTLV-1 infection have not been sufficiently studied so far. CONCLUSION: The results of this work may be helpful in determining the pathogenesis of HTLV-1-induced diseases, some types of malignancies, and in searching for new specific pharmacological agents, including molecularly targeted ones. The results of the study will help to expand the existing knowledge on the markers of MT-4 cell line.

[The effect of ferrovir on to expression of surface markers of activation by cells neoplastic line MT-4.]

The immune-modulating activity of "Ferrovir" medication in system in vitro was analyzed using neoplastic cellular line MT-4 as a model. Ferrovir decreased number of cells containing such markers of activation as CD28+, CD38+, CD62L+, CD69+ and HLA-DR+.Under 24 hours incubation period of cells in presence of 500 mkg per ml of medication, indices of decreasing of number of cells expressing these proteins (IRE), for proteins CD28, CD38, CD62L and HLA-DR made up to 1,9 ± 0,4, 1,3 ± 0,4, 1,2 ± 0,4, 1,1 ± 0,06 correspondingly. At prolonged incubation of cells in presence of Ferovir, the maximal effect was observed after 7 days of incubation and IRE for proteins mentioned above made up to 3,2, 3,4, 6,2, 1,4 и 3,1 correspondingly. Only for protein CD62L was marked a significant decreasing of number of cells bringing this marker and at 11th day of cells cultivation in presence of Ferrovir (IRE 3.89). It is possible that such an action of Ferrovir can decrease the process of spreading of cells containing integrated pathogenic material through organs and tissues of organism and slow down generalization of infectious process. The obtained results indicate that Ferrovir has an immune-modulating activity in vitro since it can decrease activating potential of neoplastic line of cells MT-4. These features can be useful in treatment of various type of cancer, HIV-infection and other human diseases. The decreasing of level of activation of cells of immune system also decreases risk of development of opportunistic infections.

[Activity of "Ferrovir" preparation towards RNA and DNA viruses]. / Aktivnost' preparata "Ferrovir" v otnoshenii RNK- i DNK- soderzhashchikh virusov.

Ferrovir (trivalent iron in complex with native sturgeon milt DNA) is nontoxic, its 50% inhibiting concentration (IC50) is at least 4000 micrograms/ml, 90% effective concentration (EC90) towards HIV-1 is 800 micrograms/ml. These effects do not depend on the cell culture or individual biological characteristics and subtypes of 7 strains of HIV-1 used in our study. The chemotherapeutic index of the drug is more than 20. Combined therapy with ferrovir and retrovir had an additive antiviral effect. Ferrovir reduced the titer of human CMV in fibroblast culture by 1-2 Ig TCD50. Ferrovir protected mice after intracerebral inoculation with lethal herpes simplex virus (type 1) (survival 33.7%, protection 27.1%, which is close to the reference group treated with zovirax). These facts evidence antiviral activity of ferrovir towards RNA and DNA viruses and prompt further study of this drug with the aim of its clinical application.

[The dependence of the biological activity of metal complexes on the structural stability of the initial DNA]. / Zavisimost' biologicheskoi aktivnosti metallokompleksov ot stabil'nosti struktury iskhodnoi DNK.

The authors have formulated the basic principles of the creation of metallo-constructions with DNA which possess biological activity. Thus, the interaction of metal and DNA during formation of metallo-construction must not destabilize the structure of initial DNA. The studies conducted by the authors prove the hypothesis of the working mechanism of these complexes: pronounced activity against viruses which contain DNA and RNA.