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Increased pro-inflammatory phenotype of peripheral blood monocytes and monocyte-derived macrophages among patients with excessive ethanol intake

ABSTRACT: Excessive alcohol consumption adversely affects the immune system and triggers the activation of peripheral blood (PB) monocytes and tissue macrophages, contributing to alcohol- related organ damage. This study aimed to analyze the M1/M2 and inflammatory phenotypes of circulating monocytes and macrophage-derived monocytes (MDMs). This single-center cross- sectional study included 20 excessive alcohol drinkers (EADs) and 22 healthy controls. PB samples were collected under fasting conditions for isolation of CD14+ monocytes and short-term culture without stimulation, LPS/IFNγ, or IL4/IL13. These conditions were also used to polarize monocyte-derived macrophages (MDMs) into M0, M1, or M2 phenotypes. Cytokine production was assessed in the blood samples and supernatants. M1/M2 related markers in PB monocytes and MDMs were analyzed using mRNA expression and surface marker analyses. In addition, the miRNA profile was analyzed in CD14+ monocytes. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines.

ORGANISM(S): Merkel cell polyomavirus Rattus norvegicus Mus musculus Human gammaherpesvirus 8 JC polyomavirus Betapolyomavirus macacae Homo sapiens Human immunodeficiency virus 1 Human betaherpesvirus 5 Human alphaherpesvirus 2 Betapolyomavirus hominis Human alphaherpesvirus 1 Murid gammaherpesvirus 4 human gammaherpesvirus 4 Mus musculus cytomegalovirus 2 Murid betaherpesvirus 1

PROVIDER: GSE239659 | GEO | 2023/10/04

REPOSITORIES: GEO

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Project description:A major population of placenta macrophages represented throughout the pregnancy consists of CD14+ macrophages, but their characteristics remain badly understood. Here we purified from placentas at term CD14+ macrophages using positive selection. The phenotyping of CD14+ macrophages performed using flow cytometry revealed that placenta CD14+ macrophages expressed a series of markers distinct of those of circulating monocytes monocyte-derived macrophages. Placenta CD14+ macrophages spontaneously matured in multinucleated giant cells (MGCs) as demonstrated by size, number of nuclei display and specific cytoskeleton organization. Placenta CD14+ macrophages and MGCs were phagocytic cells but the potential of MGCs to mount an inflammatory response was lower than that of their precursors. Placenta CD14+ macrophages and MGCs stimulated with interferon and interleukin-4 were not polarized into typical M1 or M2 profiles. Placenta macrophages exhibited specific activation transcriptional programs. Indeed, principal component analysis and hierarchical clustering show that placental macrophages formed a distinct group from circulating monocytes and monocyte-derived macrophages. Among placenta macrophages, it was also possible to distinguish CD14+ macrophages and MGCs. In addition, networks based on gene interactions were clearly different in CD14+ macrophages and MGCs. Finally, the microenvironment of placenta CD14+ macrophages governs their differentiation into MGCs because CD14+ macrophages incubated with trophoblasts exhibited exarcerbated characteristics of MGCs and because the co-incubation of circulating monocytes from working women with trophoblast supernatants resulted into the formation of MGCs whereas monocytes from non-pregnant women incubated with trophoblast supernatants did not differentiate into MGCs. Taken together, these results clearly demonstrated specific feaures of placenta CD14+ macrophages. Three replicates of each of the following: 1. Placental macrophages just after isolation (CD14+ macrophages) 2. Placental macrophages after 9 days in culture (MGCs) 3. CD14+ cells isolated from PBMC which are extracted from the whole human blood of healthy donors (Monocytes) 4. Macrophages derived from monocytes (MDMs)

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Increased pro-inflammatory phenotype of peripheral blood monocytes and monocyte-derived macrophages among patients with excessive ethanol intake

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