Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages
Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position b...
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doaj-fdec2cda4b5c436d95fed58be0bff4752021-04-28T06:01:39ZengElsevierJournal of Lipid Research0022-22752010-08-0151821912201Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophagesKonstantinos P. Markakis0Maria K. Koropouli1Stavroula Grammenou-Savvoglou2Ewoud C. van Winden3Andromaxi A. Dimitriou4Constantinos A. Demopoulos5Alexandros D. Tselepis6Eleni E. Kotsifaki7Department of Experimental Physiology, University of Athens Medical School, Athens, Greece; 2nd Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Centre, Attikon University Hospital, University of Athens Medical School, Athens, GreeceDepartment of Experimental Physiology, University of Athens Medical School, Athens, GreeceDepartment of Pathologic Physiology, University of Athens Medical School, Athens, GreeceRegulon AE, Athens, GreeceDepartment of Chemistry, University of Ioannina, Ioannina, GreeceFaculty of Chemistry, University of Athens, Athens, GreeceDepartment of Chemistry, University of Ioannina, Ioannina, GreeceTo whom correspondence should be addressed; Department of Experimental Physiology, University of Athens Medical School, Athens, GreeceRecognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A2 (Lp-PLA2) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA2 in the uptake of oxLDL by mouse peritoneal macrophages. LDL with intact Lp-PLA2 activity [LDL (+)] and LDL with completely inhibited Lp-PLA2 activity [LDL (-)] were subjected to oxidation with 5 μM CuSO4 for 6 h [moderately oxLDL (MoxLDL)], or 24 h [heavily oxLDL (HoxLDL)] and peritoneal macrophages were incubated with these preparations. The uptake of MoxLDL(-) was about 30% increased compared with that of MoxLDL(+), and HoxLDL(-) uptake was about 20% increased compared with that of HoxLDL(+). Inhibition of Lp-PLA2 activity had no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+). Liposomes prepared from the lipid extract of MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+) exhibited a similar pattern to that observed in the uptake of the corresponding intact lipoproteins. This study suggests that the progressive inactivation of Lp-PLA2 during LDL oxidation leads to an increased uptake of oxLDL by macrophages, which could be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxLDL.http://www.sciencedirect.com/science/article/pii/S0022227520370553oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholinelysophosphatidylcholinemoderately oxidized LDLheavily oxidized LDL |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Konstantinos P. Markakis Maria K. Koropouli Stavroula Grammenou-Savvoglou Ewoud C. van Winden Andromaxi A. Dimitriou Constantinos A. Demopoulos Alexandros D. Tselepis Eleni E. Kotsifaki |
spellingShingle |
Konstantinos P. Markakis Maria K. Koropouli Stavroula Grammenou-Savvoglou Ewoud C. van Winden Andromaxi A. Dimitriou Constantinos A. Demopoulos Alexandros D. Tselepis Eleni E. Kotsifaki Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages Journal of Lipid Research oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine lysophosphatidylcholine moderately oxidized LDL heavily oxidized LDL |
author_facet |
Konstantinos P. Markakis Maria K. Koropouli Stavroula Grammenou-Savvoglou Ewoud C. van Winden Andromaxi A. Dimitriou Constantinos A. Demopoulos Alexandros D. Tselepis Eleni E. Kotsifaki |
author_sort |
Konstantinos P. Markakis |
title |
Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages |
title_short |
Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages |
title_full |
Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages |
title_fullStr |
Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages |
title_full_unstemmed |
Implication of lipoprotein associated phospholipase A2 activity in oxLDL uptake by macrophages |
title_sort |
implication of lipoprotein associated phospholipase a2 activity in oxldl uptake by macrophages |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2010-08-01 |
description |
Recognition and uptake of oxidized LDL (oxLDL) by scavenger receptors of macrophages and foam cell formation are mediated by the oxidatively modified apolipoprotein B (ApoB) and lipid moiety of oxLDL. A great amount of oxidized phosphatidylcholine (oxPC) of oxLDL is hydrolyzed at the sn-2 position by lipoprotein associated phospholipase A2 (Lp-PLA2) to lysophosphatidylcholine and small oxidation products. This study examines the involvement of Lp-PLA2 in the uptake of oxLDL by mouse peritoneal macrophages. LDL with intact Lp-PLA2 activity [LDL (+)] and LDL with completely inhibited Lp-PLA2 activity [LDL (-)] were subjected to oxidation with 5 μM CuSO4 for 6 h [moderately oxLDL (MoxLDL)], or 24 h [heavily oxLDL (HoxLDL)] and peritoneal macrophages were incubated with these preparations. The uptake of MoxLDL(-) was about 30% increased compared with that of MoxLDL(+), and HoxLDL(-) uptake was about 20% increased compared with that of HoxLDL(+). Inhibition of Lp-PLA2 activity had no effect on the uptake of ApoB-liposomes conjugates with ApoB isolated from MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+). Liposomes prepared from the lipid extract of MoxLDL(-), MoxLDL(+), HoxLDL(-), and HoxLDL(+) exhibited a similar pattern to that observed in the uptake of the corresponding intact lipoproteins. This study suggests that the progressive inactivation of Lp-PLA2 during LDL oxidation leads to an increased uptake of oxLDL by macrophages, which could be primarily attributed to the increased uptake of the oxidized phospholipids enriched lipid moiety of oxLDL. |
topic |
oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine lysophosphatidylcholine moderately oxidized LDL heavily oxidized LDL |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520370553 |
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