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

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

机构地区：[1]School of Medicine,Jiangsu University,Zhenjiang 212001,Jiangsu Province,China [2]Department of Burns and Plastic Surgery,Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215002,Jiangsu Province,China

出　　处：《Burns & Trauma》2021年第1期240-254,共15页烧伤与创伤（英文）

基　　金：supported by the National Natural Science Founda-tion of China,No.82072217,81772135;the Jiangsu Natural Science Foundation,No.BK20201178。

摘　　要：Background:Burn 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.Methods:Neutrophils 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 cellswas 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.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(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.Conclusions:Taken 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 inter

关 键 词：Severe burn Heparin binding protein MYELOPEROXIDASE Vascular leakage GLYCOCALYX 

分 类 号：R73[医药卫生—肿瘤]