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Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats

This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experime...

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Autores principales: Kono, Hiroshi, Hosomura, Naohiro, Amemiya, Hidetake, Kawaida, Hiromichi, Furuya, Shinji, Shoda, Katsutoshi, Akaike, Hidenori, Kawaguchi, Yoshihiko, Ichikawa, Daisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563402/
https://www.ncbi.nlm.nih.gov/pubmed/36706425
http://dx.doi.org/10.4049/immunohorizons.2200094
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author Kono, Hiroshi
Hosomura, Naohiro
Amemiya, Hidetake
Kawaida, Hiromichi
Furuya, Shinji
Shoda, Katsutoshi
Akaike, Hidenori
Kawaguchi, Yoshihiko
Ichikawa, Daisuke
author_facet Kono, Hiroshi
Hosomura, Naohiro
Amemiya, Hidetake
Kawaida, Hiromichi
Furuya, Shinji
Shoda, Katsutoshi
Akaike, Hidenori
Kawaguchi, Yoshihiko
Ichikawa, Daisuke
author_sort Kono, Hiroshi
collection PubMed
description This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(−) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.
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spelling pubmed-105634022023-10-23 Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats Kono, Hiroshi Hosomura, Naohiro Amemiya, Hidetake Kawaida, Hiromichi Furuya, Shinji Shoda, Katsutoshi Akaike, Hidenori Kawaguchi, Yoshihiko Ichikawa, Daisuke Immunohorizons Infectious Disease This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-α, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-α and HMGB-1 by isolated tissue macrophages (Mφs) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-α and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(−) group. Increased TNF-α and HMGB-1 production by the tissue Mφs stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue Mφs was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI. AAI 2023-01-27 /pmc/articles/PMC10563402/ /pubmed/36706425 http://dx.doi.org/10.4049/immunohorizons.2200094 Text en Copyright © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Infectious Disease
Kono, Hiroshi
Hosomura, Naohiro
Amemiya, Hidetake
Kawaida, Hiromichi
Furuya, Shinji
Shoda, Katsutoshi
Akaike, Hidenori
Kawaguchi, Yoshihiko
Ichikawa, Daisuke
Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title_full Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title_fullStr Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title_full_unstemmed Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title_short Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats
title_sort recombinant human thrombomodulin reduces mortality and acute lung injury caused by septic peritonitis in rats
topic Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563402/
https://www.ncbi.nlm.nih.gov/pubmed/36706425
http://dx.doi.org/10.4049/immunohorizons.2200094
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