Background and Aims

Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycerol-3-phosphoryocholine (Ox-PAPC) is a major phospholipid in oxidized LDL (increased in atherosclerosis and other autoimmune diseases including SLE.) Such lipids are increased in autoimmune disease as SLE and associated with disease activity and cardiovascular disease. Here, we studied the effect of Ox-PAPC on immune activation in connection with atherosclerosis and autoimmunity.

The aim is to investigate how oxidized lipids can contribue to autoimmunity.

Methods

Macrophages and T-cells from human peripheral blood or atherosclerotic plaques were stimulated with Ox-PAPC in absence or presence of mitochondrial reactive oxygen species inhibitor (mito tempo) or glutathione (GSH) inhibitor (BSO). phosphatidylcholine (PTC), GSH or oxidized glutathione (GSSG) were measured from plasma. Immune activation, apoptosis, ROS production, heat shock protein 60 (HSP60), IL-1 beta, and mitochondrial membrane potential were measured by flow cytometry and/or ELISA. The level of GSH or GSSG and phosphatidylcholine in cells or plasma of atherosclerotic patients was measured by colorimetric and fluorometric kit.

Results

Ox-PAPC induced a pro-inflammatory type of T-cell activation but also induced apoptosis at a higher concentration. The Ox-PAPC-induced-activation and apoptosis of T-cells was inhibited by the mito tempo, and the mito tempo or BSO inhibited inflammatory macrophage activation. Furthermore, mitochondrial membrane potential was increased in macrophages but not in T cells. The level of PTC, GSH and GSSG were significantly higher in atherosclerotic patients as compared to control groups.

Conclusions

OxPAPC is a cause of proinflammatory activation of T cells through a direct mechanism and of macrophages in atherosclerotic plaques. Inhibition of OxPAPC could be useful to maintain plaque stability.