Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

Aila Wirkner; Antje Vogelgesang; Ines Hegge; Anja Lange; Dirk Manfred Olbertz; Bernd Gerber; Matthias Heckmann; Johanna Ruhnau

doi:10.3390/children9101522

Preterm ETs Are Significantly Reduced Compared with Adults and Partially Reduced Compared with Term Infants

Children (Basel). 2022 Oct 5;9(10):1522. doi: 10.3390/children9101522.

Authors

Aila Wirkner¹, Antje Vogelgesang², Ines Hegge¹, Anja Lange¹, Dirk Manfred Olbertz³, Bernd Gerber⁴, Matthias Heckmann¹, Johanna Ruhnau²

Affiliations

¹ Department of Neonatology and Pediatric Intensive Care, University Medicine Greifswald, 17475 Greifswald, Germany.
² Department of Neurology, University Medicine Greifswald, 17475 Greifswald, Germany.
³ Department of Neonatology, South Clinic, University Rostock, 18059 Rostock, Germany.
⁴ Department of Obstetrics and Gynecology, South Clinic, University Rostock, 18059 Rostock, Germany.

Abstract

The release of DNA by cells during extracellular trap (ET) formation is a defense function of neutrophils and monocytes. Neutrophil ET (NET) formation in term infants is reduced compared to adults. Objective: The aim was to quantify NET and monocyte ET (MET) release and the respective key enzymes myeloperoxidase (MPO) and neutrophil elastase (NE) in preterm infants. In this prospective explorative study, ET induction was stimulated by N-formylmethionine-leucyl-phenylalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), and lipoteichoic acid (LTA) in the cord blood of preterm infants (n = 55, 23-36 weeks) compared to term infants and adults. METs were quantified by microscopy, and NETs by microscopy and flow cytometry. We also determined the MPO levels within NETs and the intracellular concentrations of NE and MPO in neutrophils. The percentage of neutrophils releasing ET was significantly reduced for preterm infants compared to adults for all stimulants, and with a 68% further reduction for PMA compared to term infants (p = 0.0141). The NET area was not reduced except for when fMLP was administered. The amount of MPO in NET-producing cells was reduced in preterm infants compared to term infants. For preterm infants, but not term infants, the percentage of monocytes releasing ETs was significantly reduced compared to healthy adults for LTA and LPS stimulation. Conclusion: In preterm infants, ETs are measurable parts of the innate immune system, but are released in a reduced percentage of cells compared to adults.

Keywords: extracellular traps; monocytes; neutrophils; preterm infant.

Grants and funding

This research was funded by Verbund Norddeutscher Universitäten (M.H., J.R., and B.G.). A.V. received funding from the University of Greifswald—Käthe-Kluth Research Group. J.R. was funded by the Gerhard-Domagk Program of the University Medicine of Greifswald.