The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure

IntroductionMultiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This s...

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Main Authors: Ping Hu, Yuan hua Lu, Wei Deng, Qi Li, Ning Zhao, Qiang Shao, Ling Wu, Xu zhen Wang, Ke jian Qian, Fen Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2023.1172529/full
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author Ping Hu
Ping Hu
Yuan hua Lu
Wei Deng
Wei Deng
Qi Li
Ning Zhao
Qiang Shao
Ling Wu
Xu zhen Wang
Xu zhen Wang
Ke jian Qian
Fen Liu
Fen Liu
author_facet Ping Hu
Ping Hu
Yuan hua Lu
Wei Deng
Wei Deng
Qi Li
Ning Zhao
Qiang Shao
Ling Wu
Xu zhen Wang
Xu zhen Wang
Ke jian Qian
Fen Liu
Fen Liu
author_sort Ping Hu
collection DOAJ
description IntroductionMultiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis.Materials and methodsThe relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils.Results and discussionOur findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29.ConclusionPatient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.
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spelling doaj.art-adeb69f6ea41436aaea2acfd8da58dd22023-05-05T06:09:54ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-05-011010.3389/fmed.2023.11725291172529The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failurePing Hu0Ping Hu1Yuan hua Lu2Wei Deng3Wei Deng4Qi Li5Ning Zhao6Qiang Shao7Ling Wu8Xu zhen Wang9Xu zhen Wang10Ke jian Qian11Fen Liu12Fen Liu13Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaMedical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaMedical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaMedical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaDepartment of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaMedical Innovation Center, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, ChinaIntroductionMultiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis.Materials and methodsThe relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils.Results and discussionOur findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29.ConclusionPatient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.https://www.frontiersin.org/articles/10.3389/fmed.2023.1172529/fullsepsisneutrophilsinfiltrationpancreatic stone proteinmultiple organ dysfunction syndrome
spellingShingle Ping Hu
Ping Hu
Yuan hua Lu
Wei Deng
Wei Deng
Qi Li
Ning Zhao
Qiang Shao
Ling Wu
Xu zhen Wang
Xu zhen Wang
Ke jian Qian
Fen Liu
Fen Liu
The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
Frontiers in Medicine
sepsis
neutrophils
infiltration
pancreatic stone protein
multiple organ dysfunction syndrome
title The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
title_full The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
title_fullStr The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
title_full_unstemmed The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
title_short The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
title_sort critical role of pancreatic stone protein regenerating protein in sepsis related multiorgan failure
topic sepsis
neutrophils
infiltration
pancreatic stone protein
multiple organ dysfunction syndrome
url https://www.frontiersin.org/articles/10.3389/fmed.2023.1172529/full
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