Oxidized low-density lipoprotein, OXPAPC, corrects defects in maturation and cytokine secretion of peripheral blood dendritic cells from sepsis patients

Int J Clin Exp Med. 2014 Aug 15;7(8):2067-73. eCollection 2014.

Abstract

Objective: To investigate the expression differences in maturation and cytokine production of dendritic cells (DCs) from sepsis patients and the effect of oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) on DCs phenotypes.

Methods: Peripheral blood mononuclear cells from 50 sepsis patients and 50 controls were cultured in the presence of GM-CSF, IL-4 and TNF-α to induce DCs maturation. DCs from sepsis patients were also treated with three different concentrations of OXPAPC. Cells were characterized with optical and electron microscopy, FACS analysis for CD1α, HLA-DR and CD86 on cell surface and ELISA analysis of IL-12p70 in the supernatant.

Results: DCs from sepsis patients had smaller cell bodies and nucleus and had almost no surface projection. DCs had similar CD1α expression in sepsis patients (86.37 ± 17.24) and controls (88.58 ± 10.05). HLA-DR expression was dramatically reduced in sepsis patients (2.74 ± 5.15) compared to controls (198.35 ± 12.04). Similarly, CD86 expression was also drastically lower in sepsis patients (14.72 ± 4.83) than controls (154.56 ± 11.56). Furthermore, OXPAPC treatment of DCs from sepsis patients increased cell surface projection, HLA-DR and CD86 surface expression and IL-12p70 secretion in a dose-dependent manner. With 40 μg/ml of OXPAPC, DCs of sepsis patients have similar phenotypes observed in healthy controls.

Conclusion: DCs from sepsis patients are defective in maturation and cytokine secretion and these defects can be corrected by OXPAPC treatment.

Keywords: DC maturation; IL-12p70; OXPAPC; Sepsis.