title: Neutrophil migration into the placenta: Good, bad or deadly?
abstract: Almost 2 decades have passed since the discovery that pregnancy is associated with a basal inflammatory state involving neutrophil activation, and that this is more overt in cases with preeclampsia, than in instances with sepsis. This pivotal observation paved the way for our report, made almost a decade ago, describing the first involvement of neutrophil extracellular traps (NETs) in a non-infectious human pathology, namely preeclampsia, where an abundance of these structures were detected directly in the placental intervillous space. Despite these remarkable findings, there remains a paucity of interest among reproductive biologists in further exploring the role or involvement of neutrophils in pregnancy and related pathologies. In this review we attempt to redress this deficit by highlighting novel recent findings including the discovery of a novel neutrophil subset in the decidua, the interaction of placental protein 13 (PP13) and neutrophils in modulating spiral artery modification, as well as the use of animal model systems to elucidate neutrophil function in implantation, gestation and parturition. These model systems have been particularly useful in identifying key components implicated in recurrent fetal loss, preeclampsia or new signaling molecules such as sphingolipids. Finally, the recent discovery that anti-phospolipid antibodies can trigger NETosis, supports our hypothesis that these structures may contribute to placental dysfunction in pertinent cases with recurrent fetal loss.
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.|b Department Rheumatology , Cantonal Hospital Aarau , Aarau , Switzerland.
authors.forename: Stavros
authors.initials: S
authors.lastname: Giaglis
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Stoikou
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.|c Polytechnic University Marche , Ancona , Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Grimolizzi
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.
authors.forename: Bibin Y
authors.initials: BY
authors.lastname: Subramanian
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.
authors.forename: Shane V
authors.initials: SV
authors.lastname: van Breda
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Hoesli
authors.affiliation: d Department of Obstetrics , University Women's Hospital Basel , Basel , Switzerland.
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.affiliation: b Department Rheumatology , Cantonal Hospital Aarau , Aarau , Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Hasler
authors.affiliation: e Lendulet Reproduction Research Group, Institute of Enzymology , Research Center for Natural Sciences; Hungarian Academy of Sciences , Budapest , Hungary.
authors.forename: Nandor Gabor
authors.initials: NG
authors.lastname: Than
authors.affiliation: a Department of Biomedicine , University Hospital Basel , Basel , Switzerland.
authors.forename: Sinuhe
authors.initials: S
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002465:Cell Movement; D005260:Female; D007113:Immunity, Innate; D008954:Models, Biological; D009504:Neutrophils / Q000166:cytology*; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011256:Pregnancy Outcome
keywords: animal model; neutrophil extracellular traps (NETs); parturition; preeclampsia; pregnancy; recurrent fetal loss