A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs

Neutrophil extracellular traps (NETs) are not only promising biomarkers of disease, but also potential therapeutic targets. Overproduction or the improper clearance of NETs has been linked to disease severity. In vitro NET degradation assays can reveal mechanisms and degradation efficiency differenc...

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Main Authors: Katherine H. Nguyen, Midori L. Wasielewski, Srilakshmi Yalavarthi, Xianggui Qu, Jason S. Knight, Shuichi Takayama
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/8/615
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author Katherine H. Nguyen
Midori L. Wasielewski
Srilakshmi Yalavarthi
Xianggui Qu
Jason S. Knight
Shuichi Takayama
author_facet Katherine H. Nguyen
Midori L. Wasielewski
Srilakshmi Yalavarthi
Xianggui Qu
Jason S. Knight
Shuichi Takayama
author_sort Katherine H. Nguyen
collection DOAJ
description Neutrophil extracellular traps (NETs) are not only promising biomarkers of disease, but also potential therapeutic targets. Overproduction or the improper clearance of NETs has been linked to disease severity. In vitro NET degradation assays can reveal mechanisms and degradation efficiency differences in diseased serum samples. There is a need for more convenient assays to increase the speed of NET degradation studies. This paper describes a simplified, lower variability mimetic assay with DNA–histone structures, referred to as surface webs, that performs functionally similarly to traditional NET degradation assays with increased scalability, ease of use, shorter preparation time, and lowered costs. The surface webs are created and dehydrated in a 96-well microplate that is shelf-stable, transportable, and viable for 30 days of storage at room temperature. The surface webs, compared to NETs, have similar shapes and distribution but lower intraplate variability while degrading with healthy serum and DNase I within the same timeframe. The assay can identify patient serum with reduced degradation capabilities. This assay opens new opportunities for NET-targeted drug discovery and studies on the role of NETs as modulators of disease.
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publishDate 2025-04-01
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spelling doaj-art-70b328b5fa0b424b80ed8eccac1c8cea2025-08-20T03:14:20ZengMDPI AGCells2073-44092025-04-0114861510.3390/cells14080615A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface WebsKatherine H. Nguyen0Midori L. Wasielewski1Srilakshmi Yalavarthi2Xianggui Qu3Jason S. Knight4Shuichi Takayama5Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USADivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Mathematics and Statistics, Oakland University, Rochester, MI 48309, USADivision of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USAWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USANeutrophil extracellular traps (NETs) are not only promising biomarkers of disease, but also potential therapeutic targets. Overproduction or the improper clearance of NETs has been linked to disease severity. In vitro NET degradation assays can reveal mechanisms and degradation efficiency differences in diseased serum samples. There is a need for more convenient assays to increase the speed of NET degradation studies. This paper describes a simplified, lower variability mimetic assay with DNA–histone structures, referred to as surface webs, that performs functionally similarly to traditional NET degradation assays with increased scalability, ease of use, shorter preparation time, and lowered costs. The surface webs are created and dehydrated in a 96-well microplate that is shelf-stable, transportable, and viable for 30 days of storage at room temperature. The surface webs, compared to NETs, have similar shapes and distribution but lower intraplate variability while degrading with healthy serum and DNase I within the same timeframe. The assay can identify patient serum with reduced degradation capabilities. This assay opens new opportunities for NET-targeted drug discovery and studies on the role of NETs as modulators of disease.https://www.mdpi.com/2073-4409/14/8/615neutrophil extracellular trapsneutrophil extracellular trap degradationassay development
spellingShingle Katherine H. Nguyen
Midori L. Wasielewski
Srilakshmi Yalavarthi
Xianggui Qu
Jason S. Knight
Shuichi Takayama
A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
Cells
neutrophil extracellular traps
neutrophil extracellular trap degradation
assay development
title A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
title_full A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
title_fullStr A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
title_full_unstemmed A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
title_short A Mimetic Assay of Neutrophil Extracellular Trap Degradation Using YOYO-1-Stained DNA-Histone Surface Webs
title_sort mimetic assay of neutrophil extracellular trap degradation using yoyo 1 stained dna histone surface webs
topic neutrophil extracellular traps
neutrophil extracellular trap degradation
assay development
url https://www.mdpi.com/2073-4409/14/8/615
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