More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches.

Hemostasis is a mechanism that stops bleeding from an injured vessel, involves multiple interlinked steps, culminating in the formation of a “clot” sealing the damaged area. Moreover, it has long been recognized that inflammation also provokes the activation of the coagulation system. However, there has been an increasing amount of evidence revealing the immune function of the hemostasis system. This review collects and analyzes the results of the experimental studies and data from clinical observations confirming the inflammatory function of hemostasis. Here, we summarize the latest knowledge of the pathways in immune system activation under the influence of coagulation factors. The data analyzed allow us to consider the components of hemostasis as receptors recognizing «foreign» or damaged «self» or/and as «self» damage signals that initiate and reinforce inflammation and affect the direction of the adaptive immune response. To sum up, the findings collected in the review allow us to classify the coagulation factors, such as Damage-Associated Molecular Patterns that break down the conventional concepts of the coagulation system.

Pathogenic microbes use arginine-metabolizing enzymes as an immune evasion strategy. In this study, the impact of streptococcal arginine deiminase (ADI) on the human peripheral blood T lymphocytes function in vitro was studied. The comparison of the effects of parental strain (Streptococcus pyogenes M49-16) with wild type of ArcA gene and its isogenic mutant with inactivated ArcA gene (Streptococcus pyogenes M49-16delArcA) was carried out. It was found that ADI in parental strain SDSC composition resulted in a fivefold decrease in the arginine concentration in human peripheral blood mononuclear cell (PBMC) supernatants. Only parental strain SDSCs suppressed anti-CD2/CD3/CD28-bead-stimulated mitochondrial dehydrogenase activity and caused a twofold decrease in IL-2 production in PBMC. Flow cytometry analysis revealed that ADI decreased the percentage of CM (central memory) and increased the proportion of TEMRA (terminally differentiated effector memory) of CD4+ and CD8+ T cells subsets. Enzyme activity inhibited the proliferation of all CD8+ T cell subsets as well as CM, EM (effector memory), and TEMRA CD4+ T cells. One of the prominent ADI effects was the inhibition of autophagy processes in CD8+ CM and EM as well as CD4+ CM, EM, and TEMRA T cell subsets. The data obtained confirm arginine’s crucial role in controlling immune reactions and suggest that streptococcal ADI may downregulate adaptive immunity and immunological memory.

Anticoagulant therapy is considered to be a treatment and prophylaxis standard for venous thrombosis (VT). Despite the high efficacy and safety of modern anticoagulants, bleeding as the side effect remains a prominent unresolved problem that can limit their use. As interrelation between immune system and coagulation is the basis of immunothrombosis, immunosuppression could be considered an alternative in the target therapy for venous thrombosis. Endothelial activation due to the blood stasis and vein wall hypoxia together with proinflammatory mediators promote essential conditions for venous thrombosis. The key points of this process are also the platelets and leukocytes activation and neutrophil extracellular traps secretion. Inhibition of intercellular interactions by the adhesion and signal molecules deletion (P-selectins, galectins, HMGB1) can fully prevent thrombosis or significantly reduce the thrombus. The same effect is observed when platelets function is suppressed by GPIbα transformation, CLEC-2 deletion or von Willebrand factor deficiency. Neutropenia contributes to a change in the thrombus structure and density, and less often prevents its formation. In addition, one of the options for the VT prevention in the experiment is the introduction of resorption mediators, which are secreted by effector cells in the process of thrombosis resolution. Target therapy appears to be a promising method based on key links in the VT pathogenesis, which may allow avoiding typical complications of anticoagulant therapy.

BACKGROUND: Endothelial dysfunction underlies the pathogenesis of many socially significant diseases. The search for new original drugs for the treatment of this condition remains an important scientific and practical task. Anti-inflammatory, anticoagulant and antioxidant effects of bivalve mollusks from the family of mussels (Mytilus edulis) hydrolysate and its derivatives have been described in different model systems. AIM: The purpose of this study was to investigate the effect of M. edulis hydrolysate on the functional activity of EA.hy926 endothelial cell line. MATERIALS AND METHODS: The viability and metabolic activity of endothelial cells were studied in MTT-test. To investigate the proliferative activity, a test with staining of cells with crystal violet dye was used. The ability of the preparation to neutralize the toxic effect of HOCl and H2O2 was evaluated using fluorescent dyes and flow cytometry. RESULTS: It was found that the preparation did not have cytotoxicity and significantly increased the proliferation of endothelial cells in dilutions from 1:10 to 1:60. The preparation had a neutralizing effect against HOCl, and in all the studied dilutions significantly increased the viability of the endothelium. The preparation was not effective against H2O2, and increased H2O2 toxic effect in the maximal studied concentration. At the same time, the anti-inflammatory effect of M. edulis hydrolysate was not confirmed in this model system. The preparation had no effect on the IL-8 production and adhesion molecule CD54 (ICAM-1) and tissue factor CD146 the expression. CONCLUSIONS: The preparation of M. edulis hydrolysate enhances the proliferation of endothelial cells and is able to neutralize HOCl toxic effects.

Введение. CD4+ Т-лимфоциты играют ключевую роль в регуляции иммунитета и важны для противоопухолевой защиты. Они представляют собой гетерогенную популяцию, что требует избирательного анализа отдельных групп. Цель. Изучение дифференцировки и субпопуляционного состава CD4+ Т-лимфоцитов периферической крови у больных неоперабельной меланомой кожи по сравнению со здоровым контролем. Материалы и методы. В исследование включено 37 больных с диссеминированной или местнораспространенной нерезектабельной формой меланомы кожи. В группу сравнения включены здоровые доноры, соответствующие по возрастному и половому составу. С использованием многоцветной проточной цитометрии в периферической крови выявляли субпопуляции CD3+CD4+ лимфоцитов (Th): Th1, Th2, Th17, Tfh, а также клетки центральной (Th СМ) и периферической памяти (Th ЕМ). В рамках общего пула EM- и CM-клеток проводили детальный анализ отдельных субпопуляций Th17- («классических» Th17, Th17.1, DN Th17 и DP Th17) и Tfh-клеток (Tfh1, Tfh2, Tfh17 и DP Tfh). Результаты. При отсутствии количественных изменений в общем пуле CD4+ T-лимфоцитов крови у больных меланомой кожи выявлен дисбаланс отдельных субпопуляций, таких как Th1/Th2 среди CD4+ T-лимфоцитов, а также среди Th EM и среди Th CM. Кроме того, было повышено содержание клеток памяти Th CM и Th EM. Также выявлены сдвиги в балансе отдельных субпопуляций Th17 EM и Tfh EM. С тяжестью заболевания коррелировали такие показатели, как увеличение содержания Th17 и снижение Tfh CM-лимфоцитов, изменение соотношения субпопуляций клеток памяти (Th наивных и Th EM) и субпопуляций Th17 CM («классических» Th17 и Th17.1). В целом это указывает на наличие в организме больных активного иммунного ответа, как клеточного (изменения Th1, Th2 и Th17), так и гуморального (сдвиги в содержании Tfh). Выводы. Изучение отдельных субпопуляций CD4+ T-лимфоцитов периферической крови у больных меланомой более информативно, чем суммарная оценка большой гетерогенной группы клеток. Некоторые из выявленных показателей могут быть в дальнейшем использованы для оценки прогноза или эффективности проводимой терапии.