Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF

Background and AimsPatients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients.Material and MethodsBlood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions.ResultsSeveral features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion.ConclusionsGenomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies.

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Eugenol prevents fMLF-induced superoxide anion production in human neutrophils by inhibiting ERK1/2 signaling pathway and p47phox phosphorylation

Scientific Reports ◽

10.1038/s41598-019-55043-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Amina Chniguir ◽

Coralie Pintard ◽

Dan Liu ◽

Pham My-Chan Dang ◽

Jamel El-Benna ◽

...

Keyword(s):

Superoxide Anion ◽

Human Neutrophils ◽

Syzygium Aromaticum ◽

Superoxide Anion Production ◽

Anion Production ◽

Reduction Assay ◽

Cytochrome C Reduction ◽

Phenolic Group ◽

Anti Oxidant ◽

Neutrophil Superoxide

AbstractEugenol is a polyphenol extracted from Syzygium aromaticum essential oil. It is known to have anti-inflammatory and chemoprotective properties as well as a potent anti-oxidant activity due the presence of its phenolic group. In this study, we examined the effects of eugenol on neutrophil superoxide production, a key process involved in innate immunity and inflammation. Superoxide anion generationin human neutrophils was measured by cytochrome c reduction assay. Western blotting was used to analyze the phosphorylation of, p47phox, MAPKinases (p38 and ERK1/2), MEK1/2 and Raf, key proteins involved in the activation of NADPH oxidase. Pretreatment of neutrophils by increasing concentrations (2.5 µg/mL–20 µg/mL) of eugenol for 30 min, inhibited significantly (p < 0.001) superoxide anion generation induced by the chemotactic peptide formyl-Met-Leu-Phe (fMLF) with an IC50 of 5 µg/mL. Phorbolmyristate acetate (PMA)-stimulated O2− production was affected only at the highest eugenol concentration (20 µg/mL). Results showed that eugenol decreased the phosphorylation of p47phox onSer-345 and Ser-328, the translocation of p47phox to the membranesand the phosphorylation of Raf, MEK1/2 and ERK1/2 proteins. Taken together, our results suggest that eugenol inhibits the generation of superoxide anion by neutrophils via the inhibition of Raf/MEK/ERK1/2/p47phox-phosphorylation pathway.

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The Effect of Hypertonic and Colloid Resuscitation on Neutrophil Superoxide Anion Production and CD11b Expression After Burn

Journal of Burn Care & Rehabilitation ◽

10.1097/00004630-200103002-00123 ◽

2001 ◽

Vol 22 ◽

pp. S108

Author(s):

J. E. Stroh ◽

N. Fazal ◽

F. Haque ◽

R. L. Gamelli ◽

M. M. Sayeed

Keyword(s):

Superoxide Anion ◽

Superoxide Anion Production ◽

Cd11b Expression ◽

Anion Production ◽

Neutrophil Superoxide

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Plasma-Mediated Stimulation of Neutrophil Superoxide Anion Production During Coronary Artery Bypass Grafting: Role of Endothelin-1

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-2007-1013129 ◽

1999 ◽

Vol 47 (03) ◽

pp. 144-147 ◽

Cited By ~ 5

Author(s):

P. Bugajski ◽

R. Kalawski ◽

M. Baliński ◽

H. Wysocki ◽

R. Olszewski ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Bypass Grafting ◽

Superoxide Anion ◽

Artery Bypass ◽

Bypass Grafting ◽

Superoxide Anion Production ◽

Anion Production ◽

Neutrophil Superoxide ◽

Stimulation Of

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Lipoxins control neutrophil superoxide anion production by regulation of polyisoprenyl diphosphate phosphatase 1 activity

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.137.2 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Troy Carlo ◽

Hermann Kalwa ◽

Bruce D Levy

Keyword(s):

Superoxide Anion ◽

Superoxide Anion Production ◽

Anion Production ◽

Neutrophil Superoxide

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The measurement of superoxide anion production by granulocytes in whole blood. A clinical test for the evaluation of phagocyte function and serum opsonic capacity

European Journal of Clinical Investigation ◽

10.1111/j.1365-2362.1983.tb00114.x ◽

1983 ◽

Vol 13 (4) ◽

pp. 363-368 ◽

Cited By ~ 62

Author(s):

P. BELLA VITE ◽

P. DRI ◽

V. DELLA BIANCA ◽

M. C. SERRA

Keyword(s):

Whole Blood ◽

Superoxide Anion ◽

Clinical Test ◽

Superoxide Anion Production ◽

Anion Production

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Superoxide anion production and degranulation of rat neutrophils in response to acetaldehyde-altered liver cell membranes

Clinical Science ◽

10.1042/cs0710313 ◽

1986 ◽

Vol 71 (3) ◽

pp. 313-318 ◽

Cited By ~ 11

Author(s):

A. J. K. Williams ◽

R. E. Barry

Keyword(s):

Liver Cell ◽

Superoxide Anion ◽

Cell Membranes ◽

Membrane Vesicles ◽

Enzyme Release ◽

Superoxide Anion Production ◽

Liver Membrane ◽

Anion Production ◽

Neutrophil Superoxide ◽

Altered Liver

1. Rat liver membrane vesicles were exposed to acetaldehyde, with or without reduction of the resultant adducts formed. 2. Superoxide anion production and degranulation of rat neutrophils, upon stimulation with the liver membrane vesicles, were measured by cytochrome c reduction before and after the addition of superoxide dismutase, and β-glucuronidase release respectively. 3. Preincubation with acetaldehyde significantly enhanced superoxide anion production by both the reduced and non-reduced membrane samples (1.7-fold and 4.4-fold, respectively). 4. Preincubation with acetaldehyde significantly enhanced degranulation (1.5-fold) of neutrophils in response to the non-reduced membranes only. The reductive process itself caused a marked increase (2.4-fold) in the ability of the membrane vesicles to stimulate degranulation. 5. Cytochalasin B, an inhibitor of phagocytosis, did not reduce degranulation, implying that it occurred as a consequence of cell surface stimulation. 6. Neutrophil superoxide anion production and lysosomal enzyme release in response to acetaldehyde-altered liver cell membranes could be an important mechanism of hepatocyte injury in alcoholic liver disease.

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