Cargando…

Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation

BACKGROUND AND AIMS: Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. METHODS: Peripheral blood monocyte surface marker (CD14, CD16, CD163,...

Descripción completa

Detalles Bibliográficos
Autores principales: Gadd, Victoria L., Patel, Preya J., Jose, Sara, Horsfall, Leigh, Powell, Elizabeth E., Irvine, Katharine M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911107/
https://www.ncbi.nlm.nih.gov/pubmed/27309850
http://dx.doi.org/10.1371/journal.pone.0157771
_version_ 1782438087490535424
author Gadd, Victoria L.
Patel, Preya J.
Jose, Sara
Horsfall, Leigh
Powell, Elizabeth E.
Irvine, Katharine M.
author_facet Gadd, Victoria L.
Patel, Preya J.
Jose, Sara
Horsfall, Leigh
Powell, Elizabeth E.
Irvine, Katharine M.
author_sort Gadd, Victoria L.
collection PubMed
description BACKGROUND AND AIMS: Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. METHODS: Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. RESULTS: The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16(+) non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. CONCLUSIONS: Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased susceptibility to infection in these patients.
format Online
Article
Text
id pubmed-4911107
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-49111072016-07-06 Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation Gadd, Victoria L. Patel, Preya J. Jose, Sara Horsfall, Leigh Powell, Elizabeth E. Irvine, Katharine M. PLoS One Research Article BACKGROUND AND AIMS: Liver and systemic inflammatory factors influence monocyte phenotype and function, which has implications for hepatic recruitment and subsequent inflammatory and fibrogenic responses, as well as host defence. METHODS: Peripheral blood monocyte surface marker (CD14, CD16, CD163, CSF1R, CCR2, CCR4, CCR5, CXCR3, CXCR4, CX3CR1, HLA-DR, CD62L, SIGLEC-1) expression and capacity for phagocytosis, oxidative burst and LPS-stimulated TNF production were assessed in patients with hepatitis C (HCV) (n = 39) or non-alcoholic fatty liver disease (NAFLD) (n = 34) (classified as non-advanced disease, compensated cirrhosis and decompensated cirrhosis) and healthy controls (n = 11) by flow cytometry. RESULTS: The selected markers exhibited similar monocyte-subset-specific expression patterns between patients and controls. Monocyte phenotypic signatures differed between NAFLD and HCV patients, with an increased proportion of CD16(+) non-classical monocytes in NAFLD, but increased expression of CXCR3 and CXCR4 in HCV. In both cohorts, monocyte CCR2 expression was reduced and CCR4 elevated over controls. CD62L expression was specifically elevated in patients with decompensated cirrhosis and positively correlated with the model-for-end-stage-liver-disease score. Functionally, monocytes from patients with decompensated cirrhosis had equal phagocytic capacity, but displayed features of dysfunction, characterised by lower HLA-DR expression and blunted oxidative responses. Lower monocyte TNF production in response to LPS stimulation correlated with time to death in 7 (46%) of the decompensated patients who died within 8 months of recruitment. CONCLUSIONS: Chronic HCV and NAFLD differentially affect circulating monocyte phenotype, suggesting specific injury-induced signals may contribute to hepatic monocyte recruitment and systemic activation state. Monocyte function, however, was similarly impaired in patients with both HCV and NAFLD, particularly in advanced disease, which likely contributes to the increased susceptibility to infection in these patients. Public Library of Science 2016-06-16 /pmc/articles/PMC4911107/ /pubmed/27309850 http://dx.doi.org/10.1371/journal.pone.0157771 Text en © 2016 Gadd et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gadd, Victoria L.
Patel, Preya J.
Jose, Sara
Horsfall, Leigh
Powell, Elizabeth E.
Irvine, Katharine M.
Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title_full Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title_fullStr Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title_full_unstemmed Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title_short Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation
title_sort altered peripheral blood monocyte phenotype and function in chronic liver disease: implications for hepatic recruitment and systemic inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911107/
https://www.ncbi.nlm.nih.gov/pubmed/27309850
http://dx.doi.org/10.1371/journal.pone.0157771
work_keys_str_mv AT gaddvictorial alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation
AT patelpreyaj alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation
AT josesara alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation
AT horsfallleigh alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation
AT powellelizabethe alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation
AT irvinekatharinem alteredperipheralbloodmonocytephenotypeandfunctioninchronicliverdiseaseimplicationsforhepaticrecruitmentandsystemicinflammation