Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video)
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 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：
DOI：10.1093/burnst/tkab030
CLC：Published：2021，
Published Online：17 September 2021，
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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, 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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