DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat

Xiu-Qi Chen; Li Tu; Qing Tang; Jia-Sen Zou; Xiang Yun; Yuan-Han Qin

doi:10.1371/journal.pone.0291592

DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat

PLoS One. 2023 Oct 31;18(10):e0291592. doi: 10.1371/journal.pone.0291592. eCollection 2023.

Authors

Xiu-Qi Chen¹, Li Tu¹, Qing Tang¹, Jia-Sen Zou¹, Xiang Yun¹, Yuan-Han Qin¹

Affiliation

¹ Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.

Abstract

Background: In the past two years, studies have found a significant increase in neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), which is correlated with the severity of the disease. NETs have been reported as an intervention target in inflammatory and autoimmune diseases. This study aimed to investigate the effect of targeted degradation of NETs using DNase I in IgAV rat model.

Methods: Twenty-four Sprague-Dawley rats were randomly divided into three groups: the IgAV model group, the DNase I intervention group and the normal control group, with an average of 8 rats in each group. The model group was established by using Indian ink, ovalbumin, and Freund's complete adjuvant. In the intervention group, DNase I was injected through tail vein 3 days before the end of established model. The circulating cell free-DNA (cf-DNA) and myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, gastric antrum and descending duodenum were detected using multiple fluorescences immunohistochemistry and Western blots. Morphological changes of the tissues were observed.

Results: After the intervention of DNase I, there was a significant reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the IgAV model group (all P<0.001). The presence of NETs in renal, gastric, and duodenal tissues of the intervention group exhibited a significant decrease compared to the IgAV model group (P < 0.01). Moreover, the intervention group demonstrated significantly lower levels of renal MPO and citrullinated histone H3 (citH3) protein expression when compared to the IgAV model group (all P < 0.05). The HE staining results of intervention group demonstrated a significant reduction in congestion within glomerular and interstitial capillaries. Moreover, there was a notable improvement in gastric and intestinal mucosa necrosis, congestion and bleeding. Additionally, there was a substantial decrease in inflammatory cells infiltration.

Conclusion: The degradation of NETs can be targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted regulation of NETs holds potential as a therapeutic approach for IgAV.

Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA / metabolism
Deoxyribonuclease I / metabolism
Extracellular Traps* / metabolism
Humans
IgA Vasculitis*
Intestinal Diseases* / metabolism
Neutrophils / metabolism
Rats
Rats, Sprague-Dawley

Substances

Deoxyribonuclease I
DNA

Grants and funding

This study was supported by Innovation Project of Guangxi Graduate Education (NO: YCBZ2021047, CXQ); Research Basic Ability Enhancement Project of Young and Middle-aged Teachers in Guangxi Universities (NO: 2021KY0096, CXQ); Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University (CXQ), Guangxi Natural Science Foundation (no. 2020GXNSFAA297084, TQ), Guangxi Medical High-level Backbone Talent "139" Plan (No. G201901010, QYH) and the Key Laboratory of Children's Disease Research in Guangxi’s Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region (QYH, CXQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.