Dataset Information

Abnormal Macrophage Polarization in Patients with Myelodysplastic Syndrome.

ABSTRACT:

Background

This study is aimed at assessing the subsets of bone marrow macrophages in patients with myelodysplastic syndrome (MDS) and exploring the role of macrophages in the pathogenesis of MDS.

Methods

Thirty-eight newly diagnosed MDS patients were enrolled in the Department of Hematology of General Hospital of Tianjin Medical University from June 2015 to June 2016. Bone marrow monocytes and macrophage subsets (M1/M2) were detected in patients with MDS and normal controls by flow cytometry. M1 macrophages were cultured in vitro, and the expression of IL-1β and TNF-α mRNA was measured using real-time polymerase chain reaction.

Results

Compared with the normal control group, the proportion of bone marrow monocytes was higher (2.11 ± 0.93% vs. 3.66 ± 3.38%), and the mean fluorescence intensity of surface molecule CD14 was lower in the higher-risk (HR) MDS group (639.05 ± 359.78 vs. 458.26 ± 306.72, p < 0.05). The ratio of M2 macrophages to monocytes was higher in patients with HR-MDS (1.82 ± 2.47% vs. 3.93 ± 3.81%, p < 0.05). The ratio of M1 to M2 macrophages was lower in the HR-MDS group (3.50 ± 3.22 vs. 1.80 ± 0.88, p < 0.05). The expression of IL-1β and TNF-α mRNA in M1 macrophages was significantly lower in the MDS group (p < 0.05).

Conclusions

Patients with MDS had abnormal macrophage polarization, which may be involved in the alteration of bone marrow microenvironments.

SUBMITTER: Zhang G

PROVIDER: S-EPMC8286189 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundFerroptosis is a form of iron-dependent non-apoptotic cell death, with characteristics of loss of the activity of the lipid repair enzyme, glutathione (GSH) peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. The mechanism of ferroptosis in myelodysplastic syndrome (MDS) is unclear.MethodsCell viability assay, reactive oxygen species (ROS) assay, GSH assay, and GPX activity assay were performed to study the regulation of ferroptosis in MDS cells obtained from MDS patients, the iron overload model mice, and cell lines.ResultsThe growth-inhibitory effect of decitabine could be partially reversed by ferrostatin-1 and iron-chelating agent [desferrioxamine (DFO)] in MDS cell lines. Erastin could increase the cytotoxicity of decitabine on MDS cells. The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1. The concentration of hemoglobin in peripheral blood of iron overload mice was negatively correlated with intracellular Fe2+ level and ferritin concentration. Iron overload (IO) led to decreased viability of bone marrow mononuclear cells (BMMNCs), which was negatively correlated with intracellular Fe2+ level. Ferrostatin-1 partially reversed the decline of cell viability in IO groups. The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in BMMNCs of IO mice. DFO could increase the level of GSH. Ferrostatin-1 and DFO could increase the GPX4 activity of BMMNCs in IO mice. Ferrostatin-1 could significantly reverse the growth-inhibitory effect of decitabine in MDS patients. Decitabine could significantly increase the ROS level in MDS groups, which could be inhibited by ferrostatin-1 or promoted by erastin. Ferrostatin-1 could significantly reverse the inhibitory effect of decitabine on GSH levels in MDS patients. Erastin combined with decitabine could further reduce the GSH level. Erastin could further decrease the activity of GPX4 compared with the decitabine group.ConclusionFerroptosis may account for the main mechanisms of how decitabine induced death of MDS cells. Decitabine-induced ROS raise leads to ferroptosis in MDS cells by decreasing GSH level and GPX4 activity.