Differentiation Factors of M1 and M2 Subpopulations of Decidual Macrophages in Pregnant Women With Preeclampsia, Their Imbalance and Ways to Correct It

Abstract

According to the literature, inappropriate polarization of decidual macrophages is associated with abnormal pregnancy conditions such as spontaneous abortion, premature childbirth, preeclampsia, foetal growth retardation, etc.; therefore, studying the relationship between subpopulations of decidual macrophages and factors promoting their production in women with preeclampsia is of great clinical relevance. The purpose of this study was to identify the features of differentiation in subpopulations M1 and M2 of decidual macrophages in pregnant women with preeclampsia and to assess the impact of factors promoting their induction. Materials and methods. The concentrations of pro- and anti-inflammatory cytokines (TNF-α, INF-γ, IL-10) and the activity of iNOS and arginase in cervical mucus in pregnant women with preeclampsia were studied in comparison with the corresponding indicators in healthy pregnant women, with subsequent comparison of these indicators with the number of decidual macrophages M1 and M2 in the placentas of the examined women. We determined the concentration of cytokines by using immunoassay. NO synthase activity was determined by the difference in nitrite concentration before and after cervical mucus incubation. The total arginase activity was assessed by the difference in the concentration of L-ornithine before and after incubation in phosphate buffered saline, which contained L-arginine. Immunohistochemical study of macrophages M1 and M2 in placental tissue was carried out in the pathomorphological laboratory "CSD Health Care" (Kiev). A total of 62 pregnant women were examined: the control group included 30 healthy pregnant women who did not have risk factors for preeclampsia and unimpaired circulation in the uterine spiral arteries in the area of ​​the placental site at 18-20 + 6 weeks of gestation. The study group included 32 pregnant women at high risk to develop preeclampsia, with impaired circulation in the uterine spiral arteries in the area of ​​the placental site at 18-20 + 6 weeks of gestation; 14 of them then developed preeclampsia. Results. In pregnant women with preeclampsia, the balance of pro- and anti-inflammatory cytokines is impaired in favour of TNF-α and INF-γ with a decrease in IL-10 content that results in an imbalance in the activity of enzymes regulating the L-arginine metabolism with the following increase in iNOS activity. The activity of arginine is significantly reduced. In the placentas of women with preeclampsia, the content of decidual macrophages M1 phenotype is 1.7 times higher than their number in healthy women, while the content of macrophages M2 phenotype, on the contrary, goes down in 1.5 times. The study has shown that the predominance of decidual M1 macrophages in women with preeclampsia occurs due to the stimulating effect of INF-γ and the activation of inducible NO-synthase. This imbalance of decidual macrophages in favour of the M1 subpopulation is likely to cause the progression of endothelial dysfunction, manifestation of preeclampsia, and dysfunction of the placenta in the second trimester and in the early phase of the third trimester of gestation.