THE EFFECT OF KISSPEPTIN ON MONONUCLEAR CELL APOPTOSIS, PHAGOCYTIC ACTIVITY OF MONOCYTES AND NEUTROPHILS IN THE CONTEXT OF PREGNANCY

Abstract

During pregnancy, the maternal immune system undergoes a restructuring associated with the formation of immune tolerance aimed at preserving the fetus from adverse maternal immune responses and protecting both from pathogens. Suppression of the maternal adaptive immune response is compensated by an increased role of natural immunity, the main effectors of which are neutrophils and monocytes. Apoptosis also plays an important role during pregnancy, since activated cells can be dangerous for the developing fetus. Pregnancy hormones play a major role in this restructuring. The hypothalamic hormone kisspeptin-54 is produced by placental syncytiotrophoblast and can have effects on pregnant women's leukocytes, since they express a membrane kisspeptin receptor. The aim of the work is to evaluate the effect of kisspeptin-54 in concentrations characteristic of physiological pregnancy on the phagocytic activity of monocytes, neutrophils, and apoptosis of peripheral blood mononuclear cells (PBMC) in women. Phagocytic activity was assessed by the degree of bioluminescence quenching of the luminescent genetically engineered E. coli K12 TG1 lux⁺ strain. Lymphocyte apoptosis was assessed in the PBMC suspension by staining with annexin-V and propidium iodide. The number of cells in the early and late stages of apoptosis in the lymphocyte gate was determined. The direction of the kisspeptin-54 effects on phagocytosis depends on the cell type. The hormone inhibits phagocytosis of neutrophils, whose increased phagocytic potential can have fatal consequences for fetal development. Kisspeptin-54 has a directly opposite effect on the phagocytosis of monocytes, which are the main effector-regulatory cells of the uteroplacental compartment performing fetotrophic functions. Kisspeptin-54 increases the number of cells in the early and late stages of apoptosis. The decrease in phagocytic activity of neutrophils is associated with hormone-mediated apoptosis of neutrophils, since neutrophils are terminally differentiated cells programmed for apoptosis. Apparently, kisspeptin-54 is a factor that induces neutrophil apoptosis during pregnancy, which determines the decrease in their phagocytic function and prevents excessive activation that can cause harm to the mother and fetus. Thus, kisspeptin-54 regulates the functional activity of monocytes and neutrophils in different directions, ensuring a balance between protecting the mother's body from infections and the favorable development of the semi-allogeneic fetus.