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Role of oxygenated phosphatidylserine and its metabolites-lyso-phosphatidylserines produced after oxidation and hydrolysis by plasma lipoprotein-associated phospholipase A2 in clearance of apoptotic cells by macrophages: LC-ESI-MS study.

Kagan-VE; Tyurin-VA; Balasubramanian-K; Winnica-DE; Macphee-CH; Tyurina-Y
Toxicologist 2012 Mar; 126(Suppl 1):443
Peroxidized phospholipids and their metabolites are known modulators of inflammatory responses. We suggested that during apoptosis, oxidative modification of externalized on the cell surface phosphatidylserine (PS ) and its subsequent hydrolysis by LpPLA2VIIA would yield a pattern of diversified molecular products with different affinity and recognition by macrophage (PS) receptors. To make HL60 cells susceptible to oxidation we treated them with linoleic acid (LA) (100 nmol/106 cells). We found that phagocytosis of LA-enriched apoptotic HL60 cells (100 microM H2O2) by RAW 264.7 macrophages was significantly higher compared to naive apoptotic HL60 cells and was suppressed by annexin V. Using oxidative lipidomics approach we were able to detect the presence of oxidized PS species containing LA with two and three oxygens in LA-enriched apoptotic HL60 cells. Further, we determined whether treatment of LA-enriched apoptotic HL60 cells with LpPLA2VIIA will affect their phagocytosis. We found that the ability of macrophages to engulf apoptotic cells was significantly reduced after treatment of cells with LpPLA2VIIA. In addition, MS analysis revealed the presence of lyso-PS and oxygenated LA accompanied by a decrease amounts of oxidized PS (but not non-oxidized PS). Further, we oxidized C18:0/C18:2-PS (cyt c/H2O2) and integrated it into naive HL-60 cells. We found that phagocytosis of HL60 cells containing oxygenated PS on cell surface was ~two times higher compared to cells with incorporated non-oxidized PS. We suggest that oxidatively modified externalized PS and its hydrolysis products are important represents regulators of phagocytosis and inflammatory responses.
Immune-system; Immune-reaction; Phospholipids; Peroxides; Oxidative-phosphorylation; Oxidative-processes; Morphology; Cell-damage; Cell-morphology; Phagocytic-activity; Molecular-biology; Oxidation; Lipid-peroxidation; Cellular-reactions; Cellular-structures; Metabolites; Proteins
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Grant-Number-R01-OH-008282; B04252012
Source Name
The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
Performing Organization
University of Pittsburgh at Pittsburgh