We analyzed delayed effects of transplantation of nervous and hemopoietic fetal cells to patients with consequences of spinal trauma. A decrease in neurological deficit associated with pronounced improvement of functional independence was observed in 48.9% cases. The best results were observed in patients receiving cell transplantation within the first 2 years after trauma and in younger individuals. The pattern of morphological changes in the spinal cord at site of injury, severity of damage, and the method of transplantation had no appreciable effects on its delayed results.

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Innate immune cells (monocytes/macrophages, NK) can also develop immune memory, which means that these cells are trained after their first encounter with pathogens so that they exhibit a nonspecific immunological response to the same or another pathogen. Bacilli Calmette–Gu rin (BCG) induces nonspecific innate memory (trained immunity) in innate immune cells. We examined nonspecific innate memory in macrophages of BALB/c mice in response to mycobacteria with or without the RD1 region in the genome. Mice were immunized with BCG vaccine, and peritoneal macrophages were isolated on day 7, and then stimulated with bacterial lipopolysaccharide, CFP-10, or ESAT-6. In addition, mice were immunized with Mycobacterium tuberculosis uro-BCG vaccine (RD1-) and Mycobacterium tuberculosis strain H37Rv (RD1+) subcutaneously or intravenously; peritoneal macrophages were isolated and stimulated with lipopolysaccharide on day 4. Alveolar macrophages were obtained from lung explants of mice infected with Mycobacterium tuberculosis strain H37Rv mice, were expanded to confluence 70-80% and further stimulated with lipopolysaccharide. Lactate, cytokines, and glucose levels were examined in conditioned macrophage medium. Peritoneal macrophages from mice primed with BCG vaccine were shown to increase IL-1b, TNFa, and lactate production in response to CFP-6 and ESAT-10 (p < 0.05). Of note is the fact that lipopolysaccharide also increased production of IL-1b, TNFa, and also increased glucose uptake by peritoneal macrophages primed with BCG vaccine (p < 0.05). Peritoneal macrophages primed with Uro-BCG were shown to increase spontaneous production of IL-1b and decrease spontaneous production of TNFa (p < 0.05). When macrophages were primed by subcutaneous or intravenous administration of Mycobacterium tuberculosis strain H37Rv differentially affected cytokine production, by decreasing IL-1b production and increasing TNFa and IL-10, was observed. In response to lipopolysaccharide, peritoneal macrophages increased IL-1b, TNFa, IL-10 production and glucose consumption (p < 0.05). The mode of priming of macrophages with Mycobacterium tuberculosis strain H37Rv also led to multidirectional levels of cytokine production. Alveolar macrophages were shown to retain trained immunity, as they produced elevated levels of IL-1b, TNFa, and IL-10 (p < 0.05). Thus, mouse macrophages formed a trained immunity phenotype in response to different types of mycobacteria, which persists for a long time after primary contact with the pathogen, particularly in alveolar macrophages.

Cells of innate immunity, mainly monocytes/macrophages, form a long-term nonspecific immunological memory during the initial encounter with the pathogen, the so-called trained immunity. Mevalonate pathway metabolites play an important role in the formation of trained immunity. The aim of this investigation was to study the effect of modulators of mevalonate pathway, mevalonate and zoledronate, on the formation of trained immunity in human and animal monocytes/ macrophages.Material and methods. Human monocyte-like cell lines THP-1 and U-937, peritoneal macrophages of BALB/c mice were used. Trained immunity was induced in vitro by incubation of THP-1 and U-937 monocyte-like cell lines for 24 and 72 hours with inactivated Mycobacteria of BCG vaccine strain, and in vivo by intraperitoneal administration of BCG to BALB/c mice with isolation of peritoneal macrophages on day 7 after infection (lag phase). Cell hyperreactivity was assessed by response to a second stimulus with bacterial lipopolysaccharide (LPS) and mevalonate, zoledranate in the presence or absence of LPS. Lactate, cytokine (IL-1β, TNF-α, IL-10), nitric oxide and glucose level was measured in conditioned media from cells.Results and discussion. The study showed that monocyte-like cell lines THP-1 and U-937 responded differently by cytokine production, lactate, and glucose consumption to BCG stimulus in the presence or absence of lag phase. Mevalonate and zoledronate alone or in combination with LPS also stimulated cytokine production in different ways. The presence of lag phase for human monocyte-like cells is essential for the level of cytokine production and glucose consumption. Peritoneal macrophages have been shown to enhance pro-inflammatory cytokine production in response to LPS, mevalonate, and zoledronate.Conclusions. Mevalonate and zoledronate induce trained immunity in monocytes/macrophages.

1ФГБУ «Новосибирский научно-исследовательский институт туберкулеза» МЗ РФ, г. Новосибирск, РФ 2 ФГАОУ ВО «Новосибирский национальный исследовательский государственный университет (НГУ)», г. Новосибирск, РФ В обзоре дается представление об основных классах внеклеточных микровезикулярных частиц, механизмах их биогенеза и возможной роли в развитии туберкулезной инфекции. Особое внимание уделено роли апоптоза инфицированных микобактериями туберкулеза макрофагов, генерации апоптотических эктосом и участию последних в формировании противотуберкулезного иммунного ответа.Заключение: механизмы апоптотического блеббинга, собственно эктосомы и процессы клиринга этих частиц, возможно, могут стать в будущем новым инструментом патогенетической терапии туберкулеза.Ключевые слова: туберкулез, апоптоз, апоптотические тельца, эктосомы, экзосомы Для цитирования: Петренко А. Е., Шварц Я. Ш., Белогородцев С. Н. Внеклеточные микровезикулярные частицы в патогенезе туберкулеза // Туберкулёз и болезни лёгких.The review describes main classes of extracellular microvesicular particles, mechanisms of their biogenesis and their potential role in the development of tuberculosis. Special attention is paid to apoptosis of macrophages infected with tuberculous mycobacteria, generation of apoptotic ectosome and involvement of the latter into the formation of anti-tuberculosis immune response. Conclusion: mechanisms of apoptotic blebbing, ectosomes and clearing of these particles possess the potential to become a new tool within pathogenetic therapy of tuberculosis.

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Резюме. В модели длительного рабдомиолизиндуцированного повреждения почек у мышей C57Bl/6 изучали влияние холестериновой (ХС) диеты, внутрибрюшинного введения мевалоновой кислоты (Мев) и их сочетания на продукцию оксида азота (NO) перитонеальными макрофагами, а также на био-химические показатели нарушения функции почек, на выраженность альтеративно-инфильтративных изменений и на уровень нефросклероза в почечной ткани. Действие ХС, Мев и их сочетания на вы-раженность нефросклероза оценивали также в модели унилатеральной обструкции мочеточника. У нормальных животных и особенно у мышей с поражением почек продемонстрировано драматиче-ское снижение ЛПС-индуцированной продукции NO под действием ХС диеты, и в то же время зна-чительное усиление этой продукции под действием Мев. При введении Мев на фоне ХС диеты Мев частично отменял эффект ХС. Одновременно показано, что ХС диета усиливала фиброз, слабо влияя на альтеративно-инфильтративный компонент, тогда как Мев усиливал альтеративный компонент и несколько ослаблял фиброзный ответ. Сделан вывод, что ингибиторы (ХС диета) и активаторы (ме-валонат) мевалонатного биохимического пути разнонаправленно действуют на течение и исход хрони-ческой нефропатии, оппозитным образом влияя на М1-М2 поляризацию макрофагов. EffEcts of mEvalonatE pathway modulators upon rEactivity of macrophagEs in ExpErimEntal nEphrosclErosisabstract. The effects of cholesterol (Ch) diet, i.p. administration of mevalonic acid (Mev) and their combined application upon nitric oxide (NO) production in peritoneal macrophages, as well as upon biochemical characteristics of kidney function derangements, and histological parameters of tissue alterations, infiltration and fibrosis were studied in experimental model of chronic rhabdomyolysis-induced renal injury induced in C57Bl/6 mice. The effects of Ch diet, Mev and their combination on the degree of renal fibrosis were also studied in a model of unilateral ureteral obstruction. In normal animals, and, especially, in nephrotic mice, Ch diet was shown to cause a dramatic decrease of LPS-induced NO production, whereas Mev did enhance NO production significantly. Адрес для переписки:Шварц Яков Шмульевич, 630004, г. Новосибирск, ул. Урицкого, 35, кв. 7. Тел.: (3892) 229-51-57.