Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis

Johanne Sloth Lauszus,1 Peter Lykke Eriksen,1 Mette Mejlby Hansen,1 Lotte Lindgreen Eriksen,1 Debbie Lindsay Shawcross,2,3 Hendrik Vilstrup,1 Karen Louise Thomsen,1 Sidsel Stoy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Liver Studies,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lauszus JS, Eriksen PL, Hansen MM, Eriksen LL, Shawcross DL, Vilstrup H, Thomsen KL, Stoy S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	neutrophil non-alcoholic fatty liver disease non-alcoholic steatohepatitis oxidative burst cd11b Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/15c8f198772b47a6a0c79bf6b89717f1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15c8f198772b47a6a0c79bf6b89717f1
record_format	dspace
spelling	oai:doaj.org-article:15c8f198772b47a6a0c79bf6b89717f12021-11-14T19:00:30ZActivation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis1178-7023https://doaj.org/article/15c8f198772b47a6a0c79bf6b89717f12021-11-01T00:00:00Zhttps://www.dovepress.com/activation-and-functional-priming-of-blood-neutrophils-in-non-alcoholi-peer-reviewed-fulltext-article-CEGhttps://doaj.org/toc/1178-7023Johanne Sloth Lauszus,1 Peter Lykke Eriksen,1 Mette Mejlby Hansen,1 Lotte Lindgreen Eriksen,1 Debbie Lindsay Shawcross,2,3 Hendrik Vilstrup,1 Karen Louise Thomsen,1 Sidsel Stoy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, UKCorrespondence: Sidsel StoyDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, Aarhus, DenmarkEmail Sidsel_stoy@clin.au.dkIntroduction: In non-alcoholic fatty liver disease (NAFLD), neutrophils in liver infiltrates are activated, which may contribute to disease progression towards non-alcoholic steatohepatitis (NASH). However, the functional status of the blood neutrophils remains unknown and their role in the disease mechanisms is thus uncertain. We therefore characterized activation and function of blood neutrophils in patients with NAFLD in relation to clinical disease markers and the NAFLD plasma milieu.Methods: We studied 20 patients with NAFLD, among these 6 patients with NASH, and 14 healthy persons. Neutrophil activation, interleukin (IL)-8 production and oxidative burst were measured by flow cytometry on participants´ neutrophils and on healthy neutrophils exposed in vitro to plasma from the study participants.Results: Blood neutrophils from the NASH patients showed a doubling in their expression of the activation marker CD62L. Also, all NAFLD patients had 50– 100% increased expression of CD11b. Functionally, NASH neutrophils had 30% elevated IL-8 production and more than doubled spontaneous oxidative burst. In all NAFLD patients, higher spontaneous oxidative burst was associated with worse liver function. Incubation of healthy neutrophils with NAFLD plasma paradoxically slightly reduced CD62L and CD11b expression, and NASH plasma also reduced the frequency of IL-8-producing neutrophils.Conclusion: In NAFLD, blood neutrophils are activated, and in NASH also functionally primed. This suggests a progressive neutrophil aggressiveness already present with liver fat infiltration. However, NAFLD plasma in vitro, if anything, had the opposite effect on the healthy neutrophils so the NAFLD-related neutrophil activation cannot be attributed to humoral factors and remains unexplained.Keywords: neutrophil, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, oxidative burst, CD11bLauszus JSEriksen PLHansen MMEriksen LLShawcross DLVilstrup HThomsen KLStoy SDove Medical Pressarticleneutrophilnon-alcoholic fatty liver diseasenon-alcoholic steatohepatitisoxidative burstcd11bDiseases of the digestive system. GastroenterologyRC799-869ENClinical and Experimental Gastroenterology, Vol Volume 14, Pp 441-449 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neutrophil non-alcoholic fatty liver disease non-alcoholic steatohepatitis oxidative burst cd11b Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	neutrophil non-alcoholic fatty liver disease non-alcoholic steatohepatitis oxidative burst cd11b Diseases of the digestive system. Gastroenterology RC799-869 Lauszus JS Eriksen PL Hansen MM Eriksen LL Shawcross DL Vilstrup H Thomsen KL Stoy S Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
description	Johanne Sloth Lauszus,1 Peter Lykke Eriksen,1 Mette Mejlby Hansen,1 Lotte Lindgreen Eriksen,1 Debbie Lindsay Shawcross,2,3 Hendrik Vilstrup,1 Karen Louise Thomsen,1 Sidsel Stoy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 2Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 3Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, UKCorrespondence: Sidsel StoyDepartment of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, Aarhus, DenmarkEmail Sidsel_stoy@clin.au.dkIntroduction: In non-alcoholic fatty liver disease (NAFLD), neutrophils in liver infiltrates are activated, which may contribute to disease progression towards non-alcoholic steatohepatitis (NASH). However, the functional status of the blood neutrophils remains unknown and their role in the disease mechanisms is thus uncertain. We therefore characterized activation and function of blood neutrophils in patients with NAFLD in relation to clinical disease markers and the NAFLD plasma milieu.Methods: We studied 20 patients with NAFLD, among these 6 patients with NASH, and 14 healthy persons. Neutrophil activation, interleukin (IL)-8 production and oxidative burst were measured by flow cytometry on participants´ neutrophils and on healthy neutrophils exposed in vitro to plasma from the study participants.Results: Blood neutrophils from the NASH patients showed a doubling in their expression of the activation marker CD62L. Also, all NAFLD patients had 50– 100% increased expression of CD11b. Functionally, NASH neutrophils had 30% elevated IL-8 production and more than doubled spontaneous oxidative burst. In all NAFLD patients, higher spontaneous oxidative burst was associated with worse liver function. Incubation of healthy neutrophils with NAFLD plasma paradoxically slightly reduced CD62L and CD11b expression, and NASH plasma also reduced the frequency of IL-8-producing neutrophils.Conclusion: In NAFLD, blood neutrophils are activated, and in NASH also functionally primed. This suggests a progressive neutrophil aggressiveness already present with liver fat infiltration. However, NAFLD plasma in vitro, if anything, had the opposite effect on the healthy neutrophils so the NAFLD-related neutrophil activation cannot be attributed to humoral factors and remains unexplained.Keywords: neutrophil, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, oxidative burst, CD11b
format	article
author	Lauszus JS Eriksen PL Hansen MM Eriksen LL Shawcross DL Vilstrup H Thomsen KL Stoy S
author_facet	Lauszus JS Eriksen PL Hansen MM Eriksen LL Shawcross DL Vilstrup H Thomsen KL Stoy S
author_sort	Lauszus JS
title	Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
title_short	Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
title_full	Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
title_fullStr	Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
title_full_unstemmed	Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis
title_sort	activation and functional priming of blood neutrophils in non-alcoholic fatty liver disease increases in non-alcoholic steatohepatitis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/15c8f198772b47a6a0c79bf6b89717f1
work_keys_str_mv	AT lauszusjs activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT eriksenpl activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT hansenmm activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT eriksenll activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT shawcrossdl activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT vilstruph activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT thomsenkl activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis AT stoys activationandfunctionalprimingofbloodneutrophilsinnonalcoholicfattyliverdiseaseincreasesinnonalcoholicsteatohepatitis
_version_	1718428967350829056

Activation and Functional Priming of Blood Neutrophils in Non-Alcoholic Fatty Liver Disease Increases in Non-Alcoholic Steatohepatitis

Ejemplares similares