Recombinant thrombomodulin prevents acute lung injury induced by renal ischemia-reperfusion injury.
Acute Lung Injury
/ etiology
Animals
Blood Urea Nitrogen
Disease Models, Animal
HMGB1 Protein
/ blood
Histones
/ metabolism
Interleukin-6
/ blood
Kidney
/ metabolism
Lung
/ enzymology
Male
Mice
Mice, Inbred C57BL
Peroxidase
/ metabolism
Recombinant Proteins
/ biosynthesis
Reperfusion Injury
/ complications
Thrombomodulin
/ genetics
Tumor Necrosis Factor-alpha
/ blood
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 01 2020
14 01 2020
Historique:
received:
06
08
2019
accepted:
23
12
2019
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
11
11
2020
Statut:
epublish
Résumé
Acute kidney injury (AKI) complicated by acute lung injury has a detrimental effect on mortality among critically ill patients. Recently, a renal ischemia-reperfusion (IR) model suggested the involvement of histones and neutrophil extracellular traps (NETs) in the development of distant lung injury after renal IR. Given that recombinant thrombomodulin (rTM) has anti-inflammatory roles by binding to circulating histones, we aimed to clarify its effect on distant lung injury induced by AKI in a murine bilateral renal IR model. Both pretreatment and delayed treatment with rTM significantly decreased pulmonary myeloperoxidase activity, but they did not affect renal dysfunction at 24 h after renal IR. Additionally, rTM mitigated the renal IR-augmented expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and keratinocyte-derived chemokine), and vascular leakage, as well as the degree of lung damage. Intense histone accumulation and active NET formation occurred in both the kidneys and the lungs; however, rTM significantly decreased the histone and NET accumulation only in the lungs. Administration of rTM may have protective impact on the lungs after renal IR by blocking histone and NET accumulation in the lungs, although no protection was observed in the kidneys. Treatment with rTM may be an adjuvant strategy to attenuate distant lung injury complicating AKI.
Identifiants
pubmed: 31937858
doi: 10.1038/s41598-019-57205-0
pii: 10.1038/s41598-019-57205-0
pmc: PMC6959219
doi:
Substances chimiques
HMGB1 Protein
0
Histones
0
Interleukin-6
0
Recombinant Proteins
0
Thrombomodulin
0
Tumor Necrosis Factor-alpha
0
Peroxidase
EC 1.11.1.7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
289Références
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