Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome

Cell Physiol Biochem. 2015;35(1):292-304. doi: 10.1159/000369696. Epub 2015 Jan 10.

Abstract

Aim: The aim of this study was to explore whether the circulating frequency and function of myeloid-derived suppressor cells (MDSCs) are altered in patients with acute coronary syndrome (ACS).

Methods: The frequency of MDSCs in peripheral blood was determined by flow cytometry, and mRNA expression in purified MDSCs was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The suppressive function of MDSCs isolated from different groups was also determined. The plasma levels of certain cytokines were determined using Bio-Plex Pro™ Human Cytokine Assays.

Results: The frequency of circulating CD14(+)HLA-DR(-/low) MDSCs; arginase-1 (Arg-1) expression; and plasma levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-33 were markedly increased in ACS patients compared to stable angina (SA) or control patients. Furthermore, MDSCs from ACS patients were more potent suppressors of T-cell proliferation and IFN-γ production than those from the SA or control groups at ratios of 1:4 and 1:2; this effect was partially mediated by Arg-1. In addition, the frequency of MDSCs was positively correlated with plasma levels of IL-6, IL-33, and TNF-α.

Conclusions: We observed an increased frequency and suppressive function of MDSCs in ACS patients, a result that may provide insights into the mechanisms involved in ACS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / metabolism
  • Acute Coronary Syndrome / pathology*
  • Angina, Stable / metabolism
  • Angina, Stable / pathology
  • Arginase / genetics
  • Arginase / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Electrocardiography
  • Female
  • HLA-DR Antigens / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-1beta / blood
  • Interleukin-33
  • Interleukin-6 / blood
  • Interleukins / blood
  • Leukocytes, Mononuclear / cytology
  • Lipopolysaccharide Receptors / metabolism
  • Male
  • Middle Aged
  • Myeloid Cells / cytology
  • Myeloid Cells / metabolism*
  • RNA, Messenger / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / blood

Substances

  • HLA-DR Antigens
  • IL33 protein, human
  • Interleukin-1beta
  • Interleukin-33
  • Interleukin-6
  • Interleukins
  • Lipopolysaccharide Receptors
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • ARG1 protein, human
  • Arginase