Expansion of Myeloid-Derived Suppressor Cells in Patients with Acute Coronary Syndrome

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.

Activated Circulating Myeloid-Derived Suppressor Cells in Patients with Dilated Cardiomyopathy

“…As a defensive response to the pathogens near or within cardiac myocytes, activated monocytes and lymphocytes migrate to the myocardium [30]. The presence of these cells induces the production of inflammatory mediators, which activate MDSCs, drive their accumulation, and strengthen their suppressive activity [20,31]. In other words, the modified local microenvironment in the myocardium or systemic inflammation in DCM patients may motivate the expansion of MDSCs.…”

“…The analyses of flow cytometry data were performed using FlowJo7.6.1 (Treestar Inc., USA). The estimated absolute numbers of MDSCs were calculated as previously described [20,25].…”

“…As previously described [20], CD14 + HLA-DR -/low MDSCs were isolated from PBMCs using CD14 and HLA-DR microbeads (Milenyi Biotec, Germany). First, HLA-DR + cells were depleted by negative selection using an LD column according to the manufacturers' instructions.…”

“…1D). In addition, comparative analyses of the estimated absolute numbers were performed based on the lymphocyte and monocyte count as previously described [20]. Importantly, the absolute number of CD14 +…”

“…These cells can also be divided into monocytic and granulocytic populations with potentially distinct functions according to the expression of monocytic marker CD14 or granulocytic marker CD15 [12,14]. We and others have demonstrated that CD14 + HLA-DR -/low cells share multiple characteristics with MDSCs [15] and expand under a variety of pathological conditions, such as cancer [16][17][18][19], inflammation [20,21], and autoimmune diseases [22,23]. Presently, the inhibitory properties of MDSCs are thought to be mediated by a number of different mechanisms, including arginase-1 (Arg-1), inducible nitric oxidase (iNOS), transforming growth factor-beta (TGF-β), and interleukin-10 (IL-10) as well as the induction of regulatory T cells [10,23].…”