A novel CD14high CD16high subset of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS. (April 2016)

• Record Type: Journal Article
• Authors: Ruiz-Alcaraz, Antonio José; Tapia-Abellán, Ana; Fernández-Fernández, María Dolores; Tristán-Manzano, María; Hernández-Caselles, Trinidad; Sánchez-Velasco, Eduardo; Miras-López, Manuel; Martínez-Esparza, María; García-Peñarrubia, Pilar
• Is Part Of: Molecular immunology. Volume 72(2016:Apr.)
• Page Start: 28
• Page End: 36
• Publication Date: 2016-04
• Subjects: AF ascites fluid -- CCL2 chemokine (CC motif) ligand 2 -- ERK extracellular signal-regulated kinase -- GM-CSF granulocyte-macrophage colony-stimulating factor -- LPS lipopolysaccharide -- M-DM monocyte-derived macrophages -- MAPK mitogen-activated protein kinase -- MIP macrophage inflammatory protein -- NFкB nuclear factor kappa-light-chain-enhancer of activated B cells -- PKB protein kinase B -- PMN polymorphonuclear -- SBP spontaneous bacterial peritonitis -- TGF-β transforming growth factor beta -- TLR-4 toll-like receptor 4 -- TNF-α tumor necrosis factor alpha; Cirrhosis -- Ascites -- Inflammation -- Monocyte subsets -- Cell signaling -- Cytokines; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.02.012
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: First description of a CD14 high CD16 high M-DM subset in ascites fluid of cirrhotic patients. Basal hyperactivation of ERK and c-Jun correlates with CD14CD16 high expressing M-DM subsets. Basal hyperactivation of PKB correlates with CD16 low expressing M-DM. CD14 high-expressing subsets may be responsible for the enhanced response to LPS. Ascites M-DM produce higher amounts of IL-6, IL-10 and TNF-α, while lower levels of IL-1β and IL-12. Abstract: The aim of this study was to characterize monocyte-derived macrophages (M-DM) from blood and ascites of cirrhotic patients comparatively with those obtained from blood of healthy controls. The phenotypic profile based on CD14/CD16 expression was analyzed by flow cytometry. Cells were isolated and stimulated in vitro with LPS and heat killed Candida albicans . Phosphorylation of ERK, c-Jun, p38 MAPK, and PKB/Akt was analyzed by Western blotting. A novel CD14 high CD16 high M-DM subpopulation is present in ascites (∼33%). The CD14 ++ CD16 + intermediate subset is increased in the blood of cirrhotic patients (∼from 4% to 11%) and is predominant in ascites (49%), while the classical CD14 ++ CD16 − subpopulation is notably reduced in ascites (18%). Basal hyperactivation of ERK and JNK/c-Jun pathways observed in ascites M-DM correlates with CD14/CD16 high expressing subsets, while PI3K/PKB does it with the CD16 low expressing cells. In vitro LPS treatment highly increases ERK1/2, PKB/Akt and c-Jun phosphorylation, while that of p38 MAPK is decreased in M-DM from ascites compared to control blood M-DM. Stimulation of healthy blood M-DM with LPS and C. albicans induced higher phosphorylation levels of p38 than those from ascites. Regarding cytokines secretion, in vitro activated M-DM from ascites of cirrhotic patients produced significantly higher amounts of IL-6, IL-10 and TNF-α, and lower levels of IL-1β and IL-12 than control blood M-DM. In conclusion, a new subpopulation of CD14 high CD16 high peritoneal M-DM has been identified in ascites of cirrhotic patients, which is very sensitive to LPS stimulation.