BackgroundThe majority of tumors trigger macrophage reprogramming from an anti-tumor M1 phenotype towards a pro-tumor M2 phenotype. The M2 phenotype promotes tumor growth. We hypothesized that increasing the number of M1 macrophages in a tumor would limit carcinogenesis and extend the lifespan of the tumor host. The aim of this study was to verify this hypothesis in Ehrlich ascites carcinoma (EAC). The objectives were to evaluate effects of 1) EAC on a macrophage phenotype and NO-producing macrophage activity in vivo; 2) ascitic fluid from mice with EAC on a macrophage phenotype and NO-producing macrophage activity in vitro; and 3) in vitro reprogrammed M1 macrophages on lifespan of mice with EAC.Material/MethodsThe study was conducted using C57BL/6J mice.ResultsConcentration of nitrite, a stable NO metabolite and an index of NO production, was measured spectrophotometrically. Shifts of macrophage phenotype were assessed by changes in NO production as well as by amounts of CD80, a marker of M1 phenotype, and CD206, a marker of M2 phenotype. The CD markers were measured by flow cytometry. Macrophages were reprogrammed towards the M1 phenotype using two reprogramming factors: 0% FBS and 20 ng/ml IFN-γ. The study results showed that 1) EAC inhibited the macrophage NO production in vivo and reprogrammed macrophages towards the M2 phenotype; 2) ascitic fluid of mice with EAC inhibited the macrophage NO production in vitro and reprogrammed macrophages towards the M2 phenotype; and 3) injection of in vitro reprogrammed M1 macrophages into mice with EAC significantly increased the lifespan of mice.ConclusionsThese findings suggest that promising biotechnologies for restriction of tumor growth could be developed based on the in vitro macrophage reprogramming.
В статье оценивали фагоцитарную активность и эффект прайминга полиморфно-ядерных лейкоцитов крови (ПМЛ) при воздействии комплексного антигена Streptococcus pyogenes у пациентов с острыми гнойно-воспалительными заболеваниями кожных покровов и мягких тканей на фоне сахарного диабета II типа (с синдромом диабетической стопы) и без него. Исследование функциональной активности ПМЛ крови пациентов осуществлялось с помощью метода стимулированной сульфатом бария люминол-зависимой хемилюминесценции. Выявлено, что у пациентов с синдромом диабетической стопы наблюдается снижение фагоцитарной активности и ослабление эффекта прайминга ПМЛ крови по сравнению с пациентами, не имеющими нарушения углеводного обмена. Установлена отрицательная корреляция между фагоцитарной активностью, эффектом прайминга ПМЛ и уровнем гипергликемии в крови при синдроме диабетической стопы. Ключевые слова: полиморфно-ядерные лейкоциты, фагоцитарная активность, прайминг, хемилюминесценция, синдром диабетической стопы, гипергликемия.
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