Neutrophil extracellular traps enriched with IL-1β and IL-17A participate in the hepatic inflammatory process of patients with non-alcoholic steatohepatitis.
Interleukin 17A
Interleukin 1β
Liver
Neutrophils
Platelets
Steatohepatitis
Steatosis
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
04
03
2022
accepted:
24
04
2022
revised:
18
04
2022
pubmed:
4
5
2022
medline:
23
9
2022
entrez:
3
5
2022
Statut:
ppublish
Résumé
Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of various non-infectious inflammatory and thrombotic diseases. We investigated the presence and possible associations of NETs with various histopathologic parameters in patients with non-alcoholic steatohepatitis (NASH). We retrospectively assessed 20 liver biopsy specimens from patients with non-alcoholic fatty liver disease (NAFLD), including 17 specimens with NASH, and 14 control specimens. NETs were identified with confocal microscopy as extracellular structures with co-localization of neutrophil elastase (NE) and citrullinated histone-3. Interleukin-1β (IL-1β) and IL-17A were assessed with the same methodology. Histologic features of NAFLD were semi-quantitatively evaluated, and correlated with presence of NETs, neutrophil density, and platelet density/aggregates (assessed by immunohistochemistry for NE and CD42b, respectively). NETs were identified in 94.1% (16/17) of the NASH biopsy specimens; they were absent from all other NAFLD and control specimens. The presence of NETs was strongly correlated with steatosis (p = 0.003), ballooning degeneration (p < 0.001), lobular inflammation (p < 0.001), portal inflammation (p < 0.001), NAS score (p = 0.001), stage (p = 0.001), and diagnosis of NASH (p < 0.001). NETs were decorated with IL-1β and IL-17A. Platelet aggregates were much larger in NASH specimens, as compared to controls. In conclusion, NETs are implicated in the pathogenesis of NASH. Their associations with inflammation, ballooning degeneration (a hallmark of NASH), and stage emphasize their role in the disease process. In this setting, NETs provide a vehicle for IL-1β and IL-17A. In addition, platelet aggregation in hepatic sinusoids implies a role for thromboinflammation in NASH, and may explain the low peripheral blood platelet counts reported in patients with NASH.
Identifiants
pubmed: 35503185
doi: 10.1007/s00428-022-03330-7
pii: 10.1007/s00428-022-03330-7
doi:
Substances chimiques
Histones
0
Interleukin-17
0
Interleukin-1beta
0
Leukocyte Elastase
EC 3.4.21.37
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
455-465Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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