A novel CD14(high) CD16(high) subset-of peritoneal macrophages from cirrhotic patients is associated to an increased response to LPS

作者：Jose Ruiz Alcaraz Antonio; Tapia Abellan Ana; Dolores Fernandez Fernandez Maria; Tristan Manzano Maria; Hernandez Caselles Trinidad; Sanchez Velasco Eduardo; Miras Lopez Manuel; Martinez Esparza Maria; Garcia Penarrubia Pilar

来源：Molecular Immunology, 2016, 72: 28-36.

DOI：10.1016/j.molimm.2016.02.012

• Cirrhosis
• Ascites
• Inflammation
• Monocyte subsets
• Cell signaling
• Cytokines

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 (similar to 33%). The CD14(++)CD16(+) intermediate subset is increased in the blood of cirrhotic patients (similar to 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-alpha, and lower levels of IL-1 beta 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.

• 出版日期2016-4