Coordination of lymphocyte enzyme systems and resistance of mice to the action of staphylococcus toxin]

The activity of acid phosphatase and some dehydrogenases was studied in the blood peripheral lymphocytes of intact mice. Then this mice were given an intraperitoneal injection of LD50 of staphylococcus toxin; in 2 days 42 mice perished and 38 survived. The groups of survived and perished animals differed (the difference was statistically significant) by the extent of coordination of the enzymatic lymphocyte systems: the correlation of enzymatic indices in the survived animals was greater than in the perished ones. The data obtained are discussed from the aspect of a priori intoxication prognosis and the significance of the enzymatic coordination.     

Acetylcholine-induced lymphocyte mobility in intact and sensitized mice

During sensitization of BALB/c mice to protein antigen, spontaneous and acetylcholine-induced mobility of spleen lymphocytes increased, the maximum being reached on days 1-3 from the sensitization commencement. The acetylcholine-induced mobility of lymphocytes was reduced if the lymphocytes had been preexposed to the antigen. The data obtained attest to the same cellular substrate of antigen and acetylcholine effects.     

Cytotoxic antibodies against tumor cells in the blood of intact C3H mice]

Cytotoxic antibodies against mouse mammary tumour cells, L-cells and hepatoma 22a cells have been found in the serum of C3H/f and C3H/He mice over 8 months of age. Analogues antibodies were found in the serum of young and old BALB/c mice, but not in C57BL/6 mice. The cytotoxic activity of antimammary tumour cell serum has been completely abolished by its depletion by renal tissue of syngeneic and allogeneic animals.     

Epidemiologic and clinical features of infectious hepatitis in children against a background of massive prevention of the disease with microdoses of gamma-globulin]

The authors analyzed epidemiological and clinical peculiarities of infectious hepatitis in children aged under 11 years in conditions of mass-gamma-globulin prophylaxis in microdoses the last 5 years in Voronezh. It appeared that the incidence of the disease fell and that its clinical course became milder. In connection with reduction of the incidence of infectious hepatitis in the age group of under 10 years, the incidence of the disease was relatively higher in children aged from 10 to 14 years, with a tendency to levelling-out the periodic autumno-winter elevations among preschool children. Introduction of decreased gamma-globulin dose for hepatitis prophylaxis led to a lesser expenditure of the preparation and thus permitted to vaccinate more children.     

Effect of a viral infection on the cellular chromosome apparatus of mice in vitro and in vivo against a background of hydrocortisone action]

A cytogenetic investigation of murine bone marrow after hydrocortison injection has been made. High doses of hormone (50 mg/kg) provoke deteriorations in bone marrow both in the structure and in the chromosome number. A dose of 5 mg/kg has no such effect. The Koksak A13 virus does not induce cytogenetic deteriorations in mice, however, it is able to produce a big mutagenic effect on the hydrocortison background. The vaccine strain of measles virus -- Leningrad-16 -- also increases its mutagenic action on the bone marrow cell chromsome apparatus of mice affected with hydrocortison. At the same time, in the cell culture of murine kidney, hydrocortison does not induce chromosome deteriorations and even lowers the frequency of cells with deteriorations in the chromosome set during the initial days after injecting the virus culture with measles virus.     

Inhibition of the growth of a syngeneic weakly immunogenic tumor in mice resulting from exposures affecting T lymphocyte activity

Adult BALB/c mice were thymectomized, lethally irradiated and reconstituted with cells of syngeneic embryonic liver (B-mice). The growth of the syngeneic low-immunogenic tumor of spontaneous origin (Acatol) was strongly inhibited in B-mice as compared to that in intact recipients. The transplantation of the tumor to adult-thymectomized hosts 3 months after operation also resulted in marked retardation of tumor growth as compared to intact or sham-operated animals. The same effect was observed in mice preimmunized with spleen cells from tumor-bearers but not from intact donors. It is inferred that BALB/c mice possess strong non-specific factors of tumor resistance. However, they are actively suppressed by the mature immune system. Apparently, tumor cells, regardless of low immunogeneity are antigenic enough for the syngeneic host and induce a series of immune reactions, bringing about activation of T suppressors. It is assumed that attempts at immunizing a tumor host with autochthonous T suppressors might lead to a promising approach to cancer immunotherapy.     

Immuno- and erythropoiesis in mice with graft vs host disease against a background of immunodeficiency

In BALB/c mice immunodeficiency was induced by the transfer of lymphocytes immune to alloantigen. This model is one of experimental models of AIDS. The work was aimed at the study of disturbances in the immuno--and erythropoiesis in immunodeficient mice. The state of erythropoiesis was evaluated by the level of level of hemoglobin, hematocrit and the content of reticulocytes in peripheral blood, by the number of erythroid bursitis-forming units and the percentage of erythrokaryocytes in the marrow, as well as by the number of colony-forming units in the spleen by days 5 and 8. The study revealed that in BALB/c mice hypoplastic anemia, accompanied by the decreased phagocytic activity of macrophages and the reduced production of interleukin 1 and tumor necrosis factor, developed on months 5-6 of the disease. Macrophagal dysfunction was supposed to be one of the causes of hypoplastic anemia in immunodeficient mice.     

Comparative characterisitic of changes in the adrenals against a background of immunization with viral and bacterial antigens]

The effect of alcoholic typhoid vaccine and of the cultural vaccine against the tickborne encephalitis on the adrenocortical secretion in guinea pigs was studied. Functional condition of the adrenal glands was assessed histochemically. Immunization was accompanied by increase in the activity of the adrenal cortex, the most pronounced the first 3 days. Comparative analysis showed that typhoid vaccine produced a more pronounced stree on the adrenal gland function.     

The FX enzyme is a functional component of lymphocyte activation

Fucose is an essential constituent of selectin ligands. These molecules mediate the initial contact between extravasating leukocytes and endothelial cells. The generation of GDP-L-fucose by the FX enzyme is the final step of fucose biosynthesis. Recently, we demonstrated that outside-in signaling regulates the expression of the FX enzyme in certain cancer cells. The present study demonstrates that the polyclonal activation of T and B cells significantly up-regulated the expression of the FX enzyme and of the fucosylated selectin ligands sLe-x and CLA. Treatment of T cells with FX antisense oligonucleotides significantly decreased selectin ligand expression upon activation. We conclude that FX is regulated by outside-in signals also in lymphocytes and that this enzyme is involved in the biosynthesis of selectin ligands in such cells. We propose that FX takes part in the cascade of events leading to the extravasation of activated lymphocytes.     

Analysis of macromolecule alkylation in tissues of intact and tumor carrying mice]

Alkylation DNA reparation kinetics and the disintegration of alkylated RNA, proteins and lipids in liver, spleen and brain of intact and 22A hepatomic mice after a injection of 1-14C-nitrosomethylurea at a therapeutic dose are studied. The tissue studied are different in their macromolecules and lipids alkylation, in DNA reparation and RNA, protein and lipid degradation rates. Possible correlation between the time of the occurrence of DNA damages and the frequency of tumour emergence in different tissues is discussed. It is found that normal cells eliminate more rapidly degraded RNA, protein and lipid molecules and more rapidly repair DNA damages as compared with 22A hepatoma cells. It is suggested to be due to more rapid macromolecule metabolism in normal cells which specifies a selective sensitivity of tumour cells to alkylating agents and nitrosoalkylureas. The time of the occurrence of damages induced with alkylating agents and nitrosomethylureas is supposed to be a critical parameter in processes resulting in the selective sensitivity of normal and tumour cells.     

FMLP诱导的嗜中性白细胞呼吸爆发与凋亡的关系研究

The relationship between apoptosis of neutrophils and the change of their intracellular free Ca2+ concentration [Ca2+]i was studied. FMLP and A23187 were used to elevate the [Ca2+]i while BAPTA was used to deplete it. Fluorescence microscope, flow cytometry and gel electrophoresis were used to study the percentage of cell apoptosis and the change of f-actin during apoptosis. The results showed that the apoptosis was obviously inhibited by fMLP and A23187, while accelerated by BAPTA. The detection of f-actin showed that the f-actin depolymerized obviously during apoptosis. The elevation of [Ca2+]i inhibit the actin depolymerization while depletion of [Ca2+]i accelerated it. This result indicated that the apoptosis of neutrophil was obviously inhibited by [Ca2+]i elevation but accelerated by [Ca2+]i depletion.     

Endotoxic glycolipid as a potent depressor of the hepatic drug-metabolizing enzyme systems in mice.

Inhibitory effects of the endotoxic glycolipid from Salmonella minnesota R595 on hepatic drug-metabolizing enzyme activities in mice were investigated, and the depressor activity of the glycolipid in the enzyme systems was confirmed. Among degradation products of lipopolysaccharides tested, lipid A preparations derived from the mild acetic acid hydrolysates of lipopolysaccharides were the most active, but the lipid A fractions prepared from the hydrolysates with 1 N-HCl were almost inactive. A degraded polysaccharide fraction from E. coli lipopolysaccharide was inactive. The activities of the glycolipid and the lipid A preparation were markedly reduced by treatment with alkaline-hydroxylamine, mild alkali or hydrazine. The data showed that the lipid A moiety of the glycolipid may be responsible for the inhibitory activity on the hepatic drug-metabolizing enzyme systems.     

The comparative characteristics of the indices of lymphocyte and neutrophil functional activity in patients with HIV infection and chronic viral hepatitis B]

In 34 patients with human immunodeficiency virus (HIV) infection at the asymptomatic stage and 29 patients with chronic viral hepatitis B at the period of exacerbation (of these 14 patients had chronic persistent hepatitis and 15 patients had chronic active hepatitis) the complex study of the functional activity of lymphocytes and neutrophils was carried out by cytochemical methods with the simultaneous determination of the content of immunoregulating lymphocyte subpopulations. In patients with chronic active hepatitis a decrease in the percentage and the absolute number of helper T-lymphocytes and the ratio of CD4/8 in comparison with those in patients with HIV infection were revealed. At the same time patients with HIV infection exhibited more pronounced decrease in the activity of all lymphocytic enzymes under study (neutrophil esterase, acidic phosphatase and succinate dehydrogenase in lymphocytes), as well as in the activity of myeloperoxidase and the content of cation proteins and glycogen in neutrophils in comparison with patients having chronic active hepatitis.     

Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in mice

The neutrophil serine proteases cathepsin G (CG) and neutrophil elastase (NE) are involved in immune-regulatory processes and exert antibacterial activity against various pathogens. To date, their role and their therapeutic potential in pulmonary host defense against mycobacterial infections are poorly defined. In this work, we studied the roles of CG and NE in the pulmonary resistance against Mycobacterium bovis bacillus Calmette-Guérin (BCG). CG-deficient mice and even more pronounced CG/NE-deficient mice showed significantly impaired pathogen elimination to infection with M. bovis BCG in comparison to wild-type mice. Moreover, granuloma formation was more pronounced in M. bovis BCG-infected CG/NE-deficient mice in comparison to CG-deficient and wild-type mice. A close examination of professional phagocyte subsets revealed that exclusively neutrophils shuttled CG and NE into the bronchoalveolar space of M. bovis BCG-infected mice. Accordingly, chimeric wild-type mice with a CG/NE-deficient hematopoietic system displayed significantly increased lung bacterial loads in response to M. bovis BCG infection. Therapeutically applied human CG/NE encapsulated in liposomes colocalized with mycobacteria in alveolar macrophages, as assessed by laser scanning and electron microscopy. Importantly, therapy with CG/NE-loaded liposomes significantly reduced mycobacterial loads in the lungs of mice. Together, neutrophil-derived CG and NE critically contribute to deceleration of pathogen replication during the early phase of antimycobacterial responses. In addition, to our knowledge, we show for the first time that liposomal encapsulated CG/NE exhibit therapeutic potential against pulmonary mycobacterial infections. These findings may be relevant for novel adjuvant approaches in the treatment of tuberculosis in humans.