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001-es BibID:	BIBFORM103624
035-os BibID:	(WoS)000923633900005 (Scopus)85142716887
Első szerző:	Cho, Yeonhee
Cím:	Neutrophil extracellular traps contribute to liver damage and increase defective low-density neutrophils in alcoholic hepatitis / Cho Yeonhee, Bukong Terence Ndonyi, Tornai David, Babuta Mrigya, Vlachos Ioannis S., Kanata Eleni, Catalano Donna, Szabo Gyongyi
Dátum:	2023
ISSN:	0168-8278
Megjegyzések:	Background & Aims In alcoholic hepatitis (AH), inflammation and neutrophil counts correlate with poor clinical outcomes. Here, we investigated how neutrophils contribute to liver damage in AH. Methods We isolated blood neutrophils from AH patients to examine neutrophils extracellular traps (NETs) and performed RNA sequencing to explore unique characteristics. Results We found a significant increase of NET production in AH. We also observed a unique low-density neutrophil (LDNs) population in AH patients and alcohol-fed mice that was not present in healthy controls. Transcriptome analysis of peripheral LDNs and high-density neutrophils (HDNs) from AH patients revealed that LDNs exhibit a functionally exhausted phenotype, while HDNs are activated. Indeed, we found that AH HDNs have increased resting reactive oxygen species (ROS) and produce higher ROS upon LPS stimulation than control HDNs, whereas AH LDNs fail to respond to LPS. We show that LDNs are generated from HDNs after alcohol-induced NET release in vitro, and this LDN subset has decreased functionality including reduced phagocytosis. Moreover, LDNs showed reduced homing capacity and clearance by macrophage efferocytosis; therefore, dysfunctional neutrophils could remain in the circulation and liver. Depletion of both HDNs and LDNs in vivo prevented alcohol-induced NET production and liver damage in mice. Granulocyte-colony stimulating factor (G-CSF) treatment also ameliorated alcohol-induced liver injury in mice. Conclusion Neutrophils contribute to liver damage through increased NET formation which increases defective LDNs in AH. Alcohol induces neutrophil phenotype changes; HDNs are activated whereas LDNs are defective. Our findings provide mechanistic insights for therapeutic interventions in AH.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Hepatology. - 78 : 1 (2023), p. 28-44. -
További szerzők:	Bukong, Terence Ndonyi Tornai Dávid (1989-) (hepatológia, biomarker kutatás) Babuta, Mrigya Vlachos, Ioannis S. Kanata, Eleni Catalano, Donna Szabó Gyöngyi
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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