Neutrophil extracellular traps: molecular and cellular mechanisms of formation, role in the development of placental disorders and preeclampsia

Abstract

The review summarizes current understanding of neutrophil extracellular traps (NETs) and their role in the development of inflammation and thrombus formation during physiological and complicated pregnancy. The main initiation factors and molecular and cellular reactions leading to the generation of NETs are described. During gestation, various pregnancy-associated triggers (cytokines, hormones, colony-stimulating factors, etc.) contribute to increased activity of innate immune factors associated with the processes of neutrophil migration into gestational tissues, adhesion, degranulation, phagocytosis and release of extracellular neutrophil traps. It has been established that the uncontrolled aberrant generation of NETs, as well as their products, including reactive oxygen species, can exert a cytotoxic effect on maternal cells and tissues, adverse fetal effects and contribute to placental damage, resulting in such pregnancy complications as placental disorders, immunothrombosis and preeclampsia. The emergence of new data on the morphological and functional characteristics of the cellular component of innate immunity necessitates their advanced research with consideration of the functional potential and conditions for NETs formation, clarification and determination of their pathophysiological significance in normal and complicated pregnancy. It seems promising to study the possibility of assessment of the DNA traps levels for early diagnosis and prognosis of gestational complications, as well as for the development of new treatment strategies including targeted therapy.