Plasmas From Patients With Burn Injury Induce Endotheliopathy Through Different Pathways.

Autor: Keyloun JW; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia., Kelly EJ; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia., Carney BC; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Departments of Surgery and Biochemistry, Georgetown University School of Medicine, Washington, District of Columbia., Nisar S; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia., Kolachana S; Georgetown University School of Medicine, Washington, District of Columbia., Moffatt LT; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Departments of Surgery and Biochemistry, Georgetown University School of Medicine, Washington, District of Columbia., Orfeo T; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, Vermont., Shupp JW; The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, District of Columbia; Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, District of Columbia; Departments of Surgery and Biochemistry, Georgetown University School of Medicine, Washington, District of Columbia. Electronic address: Jeffrey.W.Shupp@medstar.net.
Jazyk: angličtina
Zdroj: The Journal of surgical research [J Surg Res] 2024 Nov 11; Vol. 304, pp. 90-100. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1016/j.jss.2024.10.011
Abstrakt: Introduction: The contribution of endothelial injury to the pathogenesis of burn shock is not well characterized. This work investigates potential mechanisms underlying dysregulation of endothelial barrier function by burn patient plasmas.
Methods: Plasma was collected from burn-injured patients (n = 8) within 4 h of admission. Demographic and injury characteristics were collected and markers of injury severity including international normalized ratio, activated partial thromboplastin time, and levels of syndecan-1 and interleukin (IL)-6, IL-1B, IL-10, Il-12p70, and tumor necrosis factor-α measured. Human umbilical vein endothelial cell monolayers (HUVEC-m) exposed to either burn patient plasma or multidonor plasma (HHP) were assessed for permeability (40 kDa fluorescein isothiocyanate (FITC)-Dextran diffusion), intercellular gap area (F-actin staining) and incidence of apoptosis (TUNEL assay). Post plasma exposure, RNA was isolated and used in polymerase chain reaction (PCR) arrays targeting genes relevant to cytoskeletal structure or apoptosis. Differences between HHP and burn plasma-treated HUVEC-m were analyzed.
Results: Five plasmas promoted significant increases in HUVEC-m permeability. When plasmas were grouped based on their capacity to increase permeability, no differences in age, %total body surface area, gender, hospital mortality, international normalized ratio, activated partial thromboplastin time, or cytokine concentration were observed; however, significantly higher syndecan-1 levels were seen in the plasmas inducing increased permeability. Increases in intercellular gap area and apoptosis and relevant gene expression were observed after exposure to patient plasmas but none of these metrics correlated completely with the pattern or magnitude of the changes in permeability.
Conclusions: Burn patient plasmas variably disrupt HUVEC-m homeostasis, differentially inducing changes in permeability, intercellular gap area, and apoptosis. Neither increases in intercellular gap size nor apoptosis appear sufficient to explain the pattern of changes in permeability.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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