Abstract

Many patients with coronary artery disease (CAD) suffer from low-grade chronic inflammation indicating an increased risk of recurrent cardiac events. The inflammatory state in CAD has been associated with elevated neutrophil counts, but also with a deficiency of regulatory T-cells (T regs ). The role of T regs in the regulation of neutrophil survival has been proposed recently. Here, we hypothesised that the interaction between T regs and neutrophils might be altered in CAD patients, and specifically investigated the impact of T regs on neutrophil apoptosis. Blood was collected from 20 CAD patients (mean age 65, 50% female) and 19 controls (mean age 64, 53% female). Neutrophils and T regs were isolated by density gradient centrifugation. Autologous neutrophils and T regs were then cocultured at ratios 1:0, 10:1, 4:1 and 1:1 for 5 h. Apoptosis (Annexin V + SYTOX staining) of neutrophils was assessed by flow cytometry. In controls, neutrophils showed increased apoptosis in a dose-dependent manner (p=0.005) when co-cultured with T regs (Figure 1A). Neutrophil apoptosis was significantly lower in patients than in controls at all ratios, (1:0, 10:1, 4:1, p< 0.05, and 1:1, p=0.01). Moreover, T regs did not affect neutrophil apoptosis in patients at any ratio (Figure 1B). To conclude, neutrophils from CAD patients were less prone to apoptosis compared to neutrophils from controls. T regs from patients were also less capable of inducing neutrophil apoptosis. Disrupted interaction between neutrophils and T regs may be a driving force of chronic inflammation in CAD patients.

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