Characteristics of Humoral Regulation of Differentiation of Bone Marrow Monocyte Subpopulations in Patients with Ischemic Cardiomyopathy

Abstract

Background: Monocytes and macrophages play an important role in atherogenesis and myocardial remodeling. Impaired differentiation of monocyte subpopulations may contribute to ischemic cardiomyopathy (ICMP). The aim of the present research was to study the features of the humoral cytokine-dependent regulation of differentiation of classical, intermediate, non-classical and transitional monocytes in bone marrow (BM) of CHD patients with or without ICMP. Materials and Methods: Forty-five patients with coronary heart disease (CHD), with and without ICMP (19 and 26 male patients, respectively), were examined. Subpopulations of classical (CD14 ++ CD16-), intermediate (CD14 ++ CD16 +), non-classical (CD14 + CD16 +), and transitional (CD14 + CD16-) monocytes in bone marrow (BM) samples were quantified by flow cytometry. Concentrations of IL-1β, IL-13, TNF-α, IFN-γ, and M-CSF in BM supernatants and blood plasma were evaluated by ELISA. Results: Concentrations of all cytokines in the blood and IL-1β, IL-13, TNF-α, М-CSF in BM supernatants as well as the capacity of М-CSF to activate, and IL-13 to inhibit, differentiation of classical monocytes from intermediate forms-were not dependent on the clinical form of CHD. Monocytopoiesis in ICMP was characterized by elevated BM concentration of IFN-γ, low М-CSF/IL-13 ratio, and a decreased percentage of classical and intermediate monocytes, accompanied by an increased number of transitional cells in BM, as compared to patients without ICMP. Conclusion: Excess of IFN-γ and low M-CSF/IL-13 ratio in BM were associated with inhibition of differentiation of mature monocyte forms and development of ICMP.

Galectin 3 and non-classical monocytes of blood as myocardial remodeling factors at ischemic cardiomyopathy

“…Transitional monocytes are probably bone marrow precursors of classical and intermediate cells, since the number of these forms in medullary tissue is negatively correlated with a number of transitional monocytes [23] , and the content of the latter is higher in the bone marrow than in blood [22] .…”

“…On the other hand, the precursors of macrophages, blood monocytes, are cells available for phenotyping. Taking into account the immunophenotypic and functional heterogeneity of monocytes and the existence of classical, intermediate, non-classical [15] , [20] and transitional [21] , [22] , [23] cells, changes in their subpopulation in the blood may represent the pathological process in the myocardium which makes it relevant to study monocytes subpopulations at ICMP.…”

Differentiation and subpopulation composition of VEGFR2+ cells in the blood and bone marrow in ischemic cardiomyopathy

“…При этом не исключено, что увеличение численности ПЭК в крови может быть связано и с интенсификацией их дифференциации в миелоидной ткани. M-CSF, IL-6 и TNFα могут быть вовлечены в процесс созревания ПЭК как провоспалительные цитокины, стимулирующие созревание клеток моноцитарного ряда [18], а VEGF -как цитокин, имеющий специфические рецепторы на мембране ПЭК [10,13]. Кроме того, негативное влияние на миелопоэз могут оказывать противовоспалительные цитокины, а именно продуцируемый Т-регуляторными клетками (Treg) IL-13, который индуцирует секрецию IL-10 макрофагами [19].…”