Biological effects of individually synthesized TNF-binding domain of variola virus CrmB protein.

The biological characteristics of a 17-kDa protein synthesized in bacterial cells, a TNF-binding domain (VARV-TNF-BP) of a 47-kDa variola virus CrmB protein (VARV-CrmB) consisting of TNF-binding and chemokine-binding domains, were studied. Removal of the C-terminal chemokine-binding domain from VARV-CrmB protein was inessential for the efficiency of its inhibition of TNF cytotoxicity towards L929 mouse fibroblast culture and for TNF-induced oxidative metabolic activity of mouse blood leukocytes. The results of this study could form the basis for further studies of VARV-TNF-BP mechanisms of activity for prospective use in practical medicine.

Effect of lysosomotropic form of amphotericin B on functional state of phagocytes in experimental candidiasis.

Effect of antifungal preparation amphotericin B and its lysosomotropic composition with dialdehyde-dextran on functional state of phagocytizing cells in the dynamics of granulomatous inflammation induced by C. albicans was studied on CBA mice. A stimulating effect of amphotericin B on the production of reactive oxygen species by peritoneal and bone marrow phagocytes was observed, while lysosomotropic form of the antibiotic did not stimulate generation of oxygen radicals.

Structural changes in the liver and content of steroid hormones in the blood and adrenal glands of mice with systemic candidiasis treated with a composition of amphotericin B and dialdehyde dextran.

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B.

Effect of oxidixed dextrans on oxidative and metabolic function of mouse peritoneal macrophages in vitro and in vivo.

We compared the effects of dextrans with a molecular weight of 35 kDa oxidized by chemical (OD(ch)) and radiochemical (OD(r)) methods on oxidative and metabolic functions of peritoneal macrophages from BALB/c mice in vitro and in vivo. It was found that none type of dextrans exhibits chemiluminescent properties. In vitro study showed that OD(ch) had a priming effect on mouse peritoneal macrophages, while OD(r) did not potentiate the oxidative and metabolic response of cells to zymosan. Being injected intraperitoneally, OD(r) more markedly enhanced chemiluminescent response of mouse peritoneal macrophages and reduced their viability than OD(ch). Thus, both dextrans are biocompatible, but in OD(ch) this parameter is higher.

Functional state of pulmonary macrophages after partial hepatectomy in mice.

Partial hepatectomy leads to qualitative and quantitative changes in the pulmonary compartment of the mononuclear phagocyte system during different periods after surgery. These changes have compensatory and adaptive nature because of loss and subsequent partial recovery of the hepatic compartment of the mononuclear phagocyte system.

[The proinflammatory activity of bronchoalveolar lavage fluid in patients on an exacerbation of pulmonary tuberculosis].

The proinflammatory activity of bronchoalveolar lavage fluid (BALF) was studied in 40 patients with an exacerbation of pulmonary tuberculosis, by applying the biological test system--donor blood. The supernatant of BALF was purified by milli pore filtration and added to blood, and the nitro blue tetrazolium (NBT) recovery test was carried out. Hanks (balanced salt) solution was used in the control. The proinflammatory effect of BALF was determined as the ratio of the count of diformazan-positive neutrophils in test and control samples (stimulation index (SI)). BALF with a low inflammatory activity suppressed the reaction of donor blood neutrophil-induced NBT recovery (SI < 1.0). On the contrary, BALF from patients with a high inflammation activity intensely stimulated donor neutrophil-induced NBT recovery (SI > 1.5). In patients with the high proinflammatory activity of BALF, the neutrophils obtained during bronchoalveolar lavage restored the parameters of the NBT test twice more actively than in those with a low proinflammatory activity of BALF. The findings suggest that the assessment of the proinflammatory activity of BALF determines the activity of exacerbated tuberculosis that is exudative and destructive with the purpose of optimizing immunomodulating therapy.

Effects of modified amphotericin in experimental systemic candidiasis.

Lysosomotropic composition of dialdehyde dextran and amphotericin B had a greater therapeutic effect in mice with systemic candidiasis compared to free amphotericin B. This composition normalized glucocorticoid function of the adrenal glands and decreased the severity of liver destruction at late terms of granulomatous inflammation.

[Studying leucocyte-endothelial mechanisms for diagnosis of vascular disorders in vibration disease].

The article presents pathogenetic mechanisms of microangiopathy development in vibration disease. The authors specified leucocyte-endothelial interactions in vascular dysfunction caused by local vibrations, suggested additional methods to diagnose vascular disorders in vibration disease patients.

[Leukocyte-modulating and antioxidant activity of blood serum and bronchoalveolar lavage fluid in the course of the decompression period of long crush syndrome].

We studied leukocyte-modulating activity (LMA) and antioxidant activity (AOA) of blood serum and bronchoalveolar lavage fluid (BAL) in the course of a postcompression period of crush syndrome (CS) in rats. CS was modelled by compression of the left back leg of the animal with metal vice (compression area 5 cm2, duration 4 hours). In CS decompression, LMA of both the serum and BAL was high. On decompression day 1 there was a compensatory growth of serum and BAL AOA, its fall on day 3 and 7 and recovery by day 21. Calculation of the coefficient of LMA to AOA shows imbalance between pro- and antioxidant systems with development of oxidant stress. Thus, prevalence of blood and lung LMA over AOA on intermediate stages of CS may cause stimulation of destruction in hepatic and pulmonary tissues with development of inflammatory reaction.

[Effect of stimulation and inhibition of macrophage functions on hypercholesterolemia in rats]. / Vliianie stimuliatsii i ingibirovaniia funktsii makrofagov na razvitie giperkholesterinemii u krys.

In this study we investigated the effects of zymosan and prodigiozan, the macrophage stimulators, and GdCl3, a macrophage inhibitor, on blood lipoprotein composition, activities of liver cholesterly ester (CE) metabolising enzymes, incorporation of [14C]cholesterol (C) into bile acids and accumulation and synthesis of CE in peritoneal macrophages (PM) of rats fed with C-enriched diet for 7 days. The increase of number of phagocyte cells quantity in liver and blood colony-stimulating activity in rats pretreated with intravenous injection of zymosan and prodigiozan was accompanied by reduced C content in blood low density and very low density lipoproteins (LDL and VLDL), increase of liver lysosomal CE hydrolase activity (without change of acyl-CoA:C acyltransferase and cytoplasmatic CE hydrolase activities) and incorporation of labeled C into bile acids and decrease of CE formation and accumulation in PM in rats with hypercholesterolemia. In contrast, reduction of phagocyte population in liver caused by intravenous injection of GdCl3 was accompanied by enhancement of C and CE level in blood LDL and VLDL and decrease of lysosomal CE hydrolase activity and incorporation of C into bile acids in liver of C-feeding rats. The data obtained suggest that the stimulation of mononuclear phagocyte system may lead to a decrease of plasma C via activation of LDL and VLDL catabolism and induction of bile acid synthesis in liver.

[Effect of plasma lipoproteins and apolipoprotein A-I on lipopolysaccharide-induced production of reactive oxygen metabolites by Kupffer cells of the rat]. / Vliianie plazmennykh lipoproteinov i apolipoproteina A-I na lipopolisakharid-indutsirovannuiu produktsiiu reaktivnykh metabolitov kisloroda kupferovskimi kletkami krys.

The effects of plasma lipoproteins on LPS-induced production of reactive oxygen intermediates (ROI) in Kupffer cells isolated from livers of zymosan-treated rats, have been studied. ROI production was low in normal Kupffer cells but increased 18-fold by LPS in Kupffer cells from zymosan-treated rats. However, preincubation of LPS with rat serum, low density lipoproteins, high density lipoproteins (HDL3) and apolipoprotein A-I (apoA-I) decreased the LPS-induced production of ROI by 1.2-, 1.3-, 2.8-, and 1.5-fold, respectively. In contrast, very low density lipoproteins and HDL2 had no significant effect on the LPS-induced production of ROI. These results provide evidence for LPS-HDL3 complex formation and suggest that HDL3 and apoA-I play an important role in host defense against endotoxemia and infection.

[The effect of nedocromil sodium on the luminal-dependent chemiluminescence of whole-blood leukocytes]. / Vliianie nedokromila natriia na liuminolzavisimuiu khemiliuminestsentsiiu leikotsitov tsel'noi krovi.

Nedocromil sodium in concentrations of 10(-3) to 10(-9) M dose-dependently inhibits a zymosan (2 mg/ml)-induced chemiluminescence response (CLR) of whole blood leukocytes and, to a lesser extent, phorbol myrystate acetate (PMA)-induced CLR. The count of diformazan-positive granulocytes in the zymosan-induced nitroblue tetrazolium test slightly reduced in the presence of 10(5) nedocromil sodium. PMA in a dose of 10(-9) M did not induce CLR, but brought about leukocyte priming, thus sensitizing them to secondary triggering by suboptimal zymosan concentrations (0.5 mg/ml). A subsequent stimulation of leukocytes with PMA + zymosan demonstrated that nedocromil sodium (10(-7) M) inhibited mainly priming PMA rather than the zymosan-triggering step of leukocyte activation.

[Induction of granulomatous liver inflammation by noninfectious particles]. / Induktsiia granulematoznogo vospaleniia pecheni neinfektsionnymi chastitsami.

A single intravenous injection of 0.1 mg/g of zymosan led to the formation of granuloma-type clusters of mononuclears in the liver of CBA mice or (CBA X C57B1)F1 hybrid mice. The area occupied by the granulomas grows for 3 to 9 days and then gradually diminishes so that the granulomas disappear practically in one month. Hydrocortisone injected in a dose of 125 mg/kg 2 and 24 hours before or 2 and 24 hours after zymosan inhibited the initiation of granulomas but, at the same time, led to their slower involution. Mice with zymosan-induced granulomas became hypersensitive to the derivate of an endotoxin--prodigiosin, a polysaccharide obtained from S. marcescens. After intravenous infusion of a preparation of corpuscular alkaline phosphatase (CAP) granuloma-like structures also appear in the liver of rats. In distinction from zymosan-induced granulomas they persist for a much longer time (up to 27 weeks). The first signs of CAP-induced granulomas appear in 3 days. The liver per cent by volume occupied by the granulomas gradually doubles by the 15th week and then reduces. At the same time, the number of granulomas per 1 mm3 of hepatic tissue remains practically constant for 3 to 21 weeks from the moment of the induction by CAP. Their average size grows slowly and reaches maximum by the 15th week, with significant variations. Desmine and reticular fibres accumulate in the granulomas, which is evidence of active involvement of hepatic fat-accumulating cells in their formation. The results show that resident macrophages are the triggers of granulomatous inflammation of the liver.

[The reactivity of pulmonary and hepatic macrophages in normal and prestimulated animals]. / Reaktivnost' makrofagov legkikh i pecheni normal'nykh i predvaritel'no stimulirovannykh zhivotnykh.

The rate of blood clearing of colloidal carbon increased two-fold as compared to the controls 5 days after prodigiosin injection. This was attended by intensified recruitment of macrophages into the alveoli and increase in the number of phagocytizing macrophages in the interstitium of the lungs by 1.5 times above normal. After administration of zymosan granules, the rate of colloid carbon clearance increased 1.5-fold in 5 days and 2.5-fold on the 9th day; the recruitment of macrophages into the alveoli and the number of phagocytizing macrophages in the interstitium of the lungs increased two-fold. At the same time, granuloma-type mononuclear infiltrates formed in the lungs and liver. Prodigiosin injection increases the rate of blood clearance 1.2-fold in animals stimulated by zymosan granules, while the volume of mononuclear infiltration, which acquires a diffuse character, increases 2.5-fold as compared to the value in zymosan stimulated animals. The effects of phagocyte reconciliation may be directly related to exacerbations of chronic inflammatory diseases of different localization.

[Functional restructurings of the mononuclear phagocyte system in experimental liver cirrhosis]. / Funktsional'nye perestroiki sistemy mononuklearnykh fagotsitov pri éksperimental'nom tsirroze pecheni.

In rats with CCl4-induced liver cirrhosis the clearance rate of colloid carbon particles was more than 2 times lower than in control animals. Simultaneously the uptake capacity of liver Kupffer calls falls. The number of phagocytizing liver macrophages decreased. Along with the diminished functional activity of liver macrophages in cirrhotic liver, the total number of lung and spleen macrophages increased 1.5-fold, with their uptake capacity increasing 10- and 3-fold, respectively. The nitroblue tetrazolium dye reduction and methacrylate particles uptake by alveolar macrophages in vitro rises. The liver, lung, spleen and peritoneal macrophages during liver fibrosis become less sensitive to zymosan stimulation. The incidence of zymosan-induced liver infiltrates decreases 50-fold, while in the lungs they do not develop at all. Such a decreased macrophage reactivity may be closely linked with progressing, poorly reversible liver fibrosis.