Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)

Lu Liu; Yiming Shao; Yixuan Zhang; Yunxi Yang; Jiamin Huang; Linbin Li; Ran Sun; Yuying Zhou; Yicheng Su; Bingwei Sun

doi:10.1093/burnst/tkab030

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Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)

更新时间：2022-06-14

- Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)
- Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)
- Burns & Trauma 2021年9卷第1期
- 作者机构：
  
  1. School of Medicine
  2. Jiangsu University
  3. Department of Burns and Plastic Surgery
  4. Affiliated Suzhou Hospital of Nanjing Medical University
- 作者简介：
- 基金信息：
  
  This study was supported by the National Natural Science Foundation of China, No. 82072217 and 81772135;by the Jiangsu Natural Science Foundation, No. BK20201178.
- DOI：10.1093/burnst/tkab030
  中图分类号：
- 纸质出版日期：2021，
  
  网络出版日期：2021-9-17，
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Lu Liu, Yiming Shao, Yixuan Zhang, 等. Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)[J]. Burns & Trauma, 2021,9(1).

Lu Liu, Yiming Shao, Yixuan Zhang, Yunxi Yang, Jiamin Huang, Linbin Li, Ran Sun, Yuying Zhou, Yicheng Su, Bingwei Sun, Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video), Burns & Trauma, Volume 9, 2021, tkab030, https://doi.org/10.1093/burnst/tkab030
Lu Liu, Yiming Shao, Yixuan Zhang, 等. Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)[J]. Burns & Trauma, 2021,9(1). DOI： 10.1093/burnst/tkab030.

Lu Liu, Yiming Shao, Yixuan Zhang, Yunxi Yang, Jiamin Huang, Linbin Li, Ran Sun, Yuying Zhou, Yicheng Su, Bingwei Sun, Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video), Burns & Trauma, Volume 9, 2021, tkab030, https://doi.org/10.1093/burnst/tkab030 DOI：

摘要

Abstract

BackgroundBurn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury. However

the pathophysiological mechanism of vascular leakage is still unclear. The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.MethodsNeutrophils were isolated from human peripheral blood by magnetic beads sorting. ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma. The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice

and high-quality video were provided. Adhesion-related molecules were investigated by qRT-PCR. The damage to glycocalyx of mice vascular endothelial cells was observed by transmission electron microscope and scanning electron microscope. Proteomic analysis

flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite (HOCl) and CD44 of human vascular endothelial cells.ResultsIn this study

we found that rapidly increasing activated neutrophils secrete heparin binding protein (HBP) and myeloperoxidase (MPO) after severe burn injury. Increased HBP triggers vascular leakage with synergy of MPO

results in systemic edema and burn shock. Furthermore

we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx. Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage. However

MPO inhibitors partially protect the glycocalyx of vascular endothelial cells. The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.ConclusionsTaken together

these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns. Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.

关键词

Keywords

Severe burnHeparin binding proteinMyeloperoxidaseVascular leakageGlycocalyx

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