Neutrophil Extracellular Trap Degradation by Differently Polarized Macrophage Subsets

Arteriosclerosis, Thrombosis, and Vascular Biology
Patrick HaiderPhilipp Hohensinner

Abstract

Macrophages are immune cells, capable to remodel the extracellular matrix, which can harbor extracellular DNA incorporated into neutrophil extracellular traps (NETs). To study the breakdown of NETs we studied the capability of macrophage subsets to degrade these structures in vitro and in vivo in a murine thrombosis model. Furthermore, we analyzed human abdominal aortic aneurysm samples in support of our in vitro and in vivo results. Approach and Results: Macrophages were seeded onto blood clots or isolated NETs and polarized. All macrophages were capable to degrade NETs. For initial breakdown, macrophages relied on extracellular deoxyribonucleases. Proinflammatory polarization enhanced NET degradation. The boost in degradation was because of increased macropinocytosis, as inhibition by imipramine diminished their NET breakdown. Inhibition of macropinocytosis in a murine thrombosis model led to increased NET burden and reduced thrombus resolution in vivo. When analyzing abdominal aortic aneurysm samples, macrophage density furthermore corresponded negatively with the amount of local NETs in the intraluminal thrombi as well as in the vessel wall, as increased macrophage density was associated with a reduction in NET burden. We p...Continue Reading

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Citations

Aug 28, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Kimberly Martinod
Nov 27, 2020·Frontiers in Cell and Developmental Biology·Thomas M HofbauerIrene M Lang
Apr 6, 2021·Frontiers in Cellular and Infection Microbiology·Jingyi WangMingyun Li
Jun 4, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Stella ChaushevaIrene M Lang
Aug 6, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Umesh Kumar DhawanManikandan Subramanian
Oct 28, 2021·Immunology·Apurwa Singhal, Sachin Kumar

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Methods Mentioned

BETA
flow cytometry
ELISA
ELISAs
fluorescence-activated cell sorting
Fluorescence microscopy

Software Mentioned

TissueFAXS
FIJI

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