RESUMO
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play key roles in sepsis, but whether the bone marrow is considered the only source remains unclear. The current knowledge about the mechanism of MDSCs leading to myocardial injury in sepsis is poor. METHODS: In sepsis patients with cardiac dysfunction, the circulating percentage of CD14-CD11b+ and serum concentrations of IL-6 and IL-1ß were measured. A mouse sepsis model was established through caecum ligation and puncture (CLP). Animals were divided into four groups: control, sham, CLP and CLP+splenectomy (CLPS). Serum concentrations of IL-6, IL-1ß, TnI and NT-proBNP were measured. CD11b+Gr-1+ cells were detected by immunofluorescence staining and RT-PCR. Myocardial injury was detected by HE, Masson and TUNEL staining. The expression of mTOR, P53 and caspase-3 was measured by Western blot. RESULTS: In sepsis patients, circulating MDSCs were increased, and the serum concentrations of IL-6 and IL-1ß were elevated. The serum concentrations of IL-6 and IL-1ß were correlated with the ratio of circulating MDSCs. In the mouse sepsis model, the spleen was the major source of CD11b+Gr-1+ cells that migrated into circulation and the heart in sepsis. The serum concentrations of IL-6 and IL-1ß were also elevated. Echocardiography and serum biomarkers showed that cardiomyocyte damage and cardiac hypofunction in sepsis-induced myocardial injury. The expression of CD11b, Gr-1 and pro-inflammatory cytokines in the heart was significantly higher in sepsis patients than that in controls. Pathological staining and TUNEL staining showed obvious myocardial damage and cell apoptosis. The Western blot analysis indicated that in the heart, the activation of mTOR was inhibited and that the expression of P53 and caspase-3 was elevated in sepsis-induced myocardial injury. CONCLUSION: In sepsis-induced myocardial injury, splenic reservoir CD11b+Gr-1+ cells rapidly migrated into circulation and the heart, further impairing heart function via the high expression of P53 through the inhibition of mTOR.