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Ageing Affects Neutrophils – Changes in Activation, DNA Release and Neutrophil Extracellular Formation of Neutrophil Subpopulations with Human Age

1Medical University of Vienna, Hematology and Hemostaseology, Vienna, Austria, 2Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology, Vienna, Austria, 3Medical University of Vienna, Department of Surgery, Vienna, Austria

Abstract Number: PB2015

Meeting: ISTH 2020 Congress

Theme: Vascular Biology » Innate and Adaptive Immunity

Background: The heterogeneity of neutrophils and their functions, especially production of neutrophil extracellular traps (NETs), are important foci of thrombosis research. Neutrophils can be subdivided into high and low density neutrophils (HDNs/LDNs) and they are thought to react differently to stimuli. Studies have shown differences in neutrophil subpopulations and functionality in patients but data on healthy subjects are scarce.

Aims: We aimed to investigate age-related changes in neutrophil activation, DNA release and NET formation.

Methods: HDNs and LDNs from 25 healthy individuals, subdivided in 3 age groups (< 45 years, n=8; 45-54 years, n=9; >54 years, n=8) were isolated. Potential of activation (increase of CD11b surface expression), DNA release (DNA release assay) and NET production (measured by citrullinated histone H3 (H3Cit)) of HDNs/LDNs were investigated after stimulation with ionomycin (IO) and phorbol 12-myristate 13-acetate (PMA).

Results: No differences in isolated HDN or LDN counts were observed among the age groups. HDNs from older individuals had less increase of activation markers (MFI CD11b) than HDNs from younger subjects (Fig.1A) but they showed significantly increased DNA release compared to those from younger participants (Fig.1B). NET release was higher in LDNs (Fig.1C) compared to HDNs (Fig.1D) and with regard to age groups the highest NET release at baseline but also after 3h of stimulation with IO was seen in LDNs of the age group between 45-54 years (Fig.1C).

Conclusions: We conclude that neutrophils and their ability of activation, DNA release and NET formation change during the ageing process and that this might be associated with a higher thrombotic risk and increased vulnerability to infections at advanced age. Furthermore, these results highlight the importance and necessity of correct age-matching in studies, especially in studies focusing on neutrophils.


[Figure 1: Potential of activation (A), DNA release (B) and NET formation (C/D), measured by H3Cit, in neutrophils (HDNs/LDNs) of healthy volunteers.]

To cite this abstract in AMA style:

Mauracher L-, Krall M, Roiß J, Hell L, Ondracek AS, Gebhart J, Brostjan C, Ay C, Pabinger I. Ageing Affects Neutrophils – Changes in Activation, DNA Release and Neutrophil Extracellular Formation of Neutrophil Subpopulations with Human Age [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/ageing-affects-neutrophils-changes-in-activation-dna-release-and-neutrophil-extracellular-formation-of-neutrophil-subpopulations-with-human-age/. Accessed September 24, 2023.

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