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Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics.

ABSTRACT: UNLABELLED:Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In humans, three monocyte subsets have been identified: the classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory and fibrotic liver diseases. The frequency of intrahepatic monocytes increased in disease compared with control liver tissue, and in both nondiseased and diseased livers there was a higher frequency of CD14++CD16+ cells with blood. Our data suggest two nonexclusive mechanisms of CD14++CD16+ accumulation in the inflamed liver: (1) recruitment from blood, because more than twice as many CD14++CD16+ monocytes underwent transendothelial migration through hepatic endothelial cells compared with CD14++CD16- cells; and (2) local differentiation from CD14++CD16- classical monocytes in response to transforming growth factor ? and interleukin (IL)-10. Intrahepatic CD14++CD16+ cells expressed both macrophage and dendritic cell markers but showed high levels of phagocytic activity, antigen presentation, and T cell proliferation and secreted proinflammatory (tumor necrosis factor ?, IL-6, IL-8, IL-1?) and profibrogenic cytokines (IL-13), chemokines (CCL1, CCL2, CCL3, CCL5), and growth factors (granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor), consistent with a role in the wound healing response. CONCLUSION:Intermediate CD14++CD16+ monocytes preferentially accumulate in chronically inflamed human liver as a consequence of enhanced recruitment from blood and local differentiation from classical CD14++CD16- monocytes. Their phagocytic potential and ability to secrete inflammatory and profibrogenic cytokines suggests they play an important role in hepatic fibrogenesis.

SUBMITTER: Liaskou E

PROVIDER: S-EPMC4194426 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics.

Liaskou Evaggelia E Zimmermann Henning W HW Li Ka-Kit KK Oo Ye H YH Suresh Shankar S Stamataki Zania Z Qureshi Omar O Lalor Patricia F PF Shaw Jean J Syn Wing-kin WK Curbishley Stuart M SM Adams David H DH

Hepatology (Baltimore, Md.) 20121204 1

<h4>Unlabelled</h4>Liver fibrosis is a wound healing response to chronic liver injury and inflammation in which macrophages and infiltrating monocytes participate in both the development and resolution phase. In humans, three monocyte subsets have been identified: the classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes. We studied the phenotype and function of these monocyte subsets in peripheral blood and liver tissue from patients with chronic inflammatory a ...[more]

PMID: 22911542

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Project description:BackgroundAge-associated changes in immunity are inextricably linked to chronic inflammation and age-related diseases, the impact of aging on monocyte subsets is poorly understood.MethodsFlow cytometry was applied to distinguish three monocyte subsets between 120 young and 103 aged individuals. We then analyzed the expression profiles of three monocyte subsets from 9 young and 9 older donors and CD14+ monocytes from 1202 individuals between 44 and 83 years old. Flow cytometry was used to measure β-galactosidase activities, ROS levels, mitochondrial contents, mitochondrial membrane potentials (MMPs) and intracellular IL-6 levels in three monocyte subsets of young and elderly individuals, and plasma IL-6 levels were detected by electrochemiluminescence immunoassay. Mitochondrial stress and glycolytic rate of CD14+ monocytes from young and aged individuals were measured by Seahorse XFe24 Analyzer.ResultsCompared with young individuals, the percentage of classical subset in aged persons significantly decreased, while the proportion of nonclassical subset increased. Age-related differential genes were obviously enriched in cellular senescence, ROS, oxidative phosphorylation, mitochondrial respiratory chain, IL-6 and ribosome-related pathways. Compared with young individuals, the β-galactosidase activities, ROS contents, intracellular IL-6 levels of three monocyte subsets, and plasma IL-6 levels in aged individuals were significantly elevated, while the MMPs apparently declined with age and the mitochondrial contents were only increased in intermediate and nonclassical subsets. CD14+ monocytes from elderly adults had conspicuously lower basal and spare respiratory capacity and higher basal glycolysis than those from young individuals.ConclusionsDuring aging, monocytes exhibited senescence-associated secretory phenotype, mitochondrial dysfunction, decreased oxidative phosphorylation and increased glycolysis and the nonclassical subset displayed the clearest features of aging. Our study comprehensively investigated age-related transcriptional alterations of three monocyte subsets and identified the pivotal pathways of monocyte senescence, which may have significant implications for tactics to alleviate age-related conditions.

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Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics.

Publications

Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics.

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