TY - JOUR
T1 - Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids involves activation of cPLA2 and lipoxygenase
AU - Huber, Joakim
AU - Fürnkranz, Alexander
AU - Bochkov, Valery N.
AU - Patricia, Mary K.
AU - Lee, Hans
AU - Hedrick, Catherine C.
AU - Berliner, Judith A.
AU - Binder, Bernd R.
AU - Leitinger, Norbert
PY - 2006/5
Y1 - 2006/5
N2 - Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not neutrophils, an initiating event in atherogenesis. Here, we investigate intracellular signaling events induced by oxidized phospholipids in human umbilical vein endothelial cells (HUVECs) that lead to specific monocyte adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn- glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2- oxovaleroyl-sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte adhesion was dependent on protein kinases A and C, extracellular signal-regulated kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic phospholipase A2 (cPLA2). Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids. Peroxisome proliferator-activated receptor α (PPARα) was excluded as a possible target for 12-HETE, because monocyte adhesion was still induced in endothelial cells from PPARα null mice. Together, our results suggest that oxidized phospholipids stimulate HUVECs to specifically bind monocytes involving MAPK pathways, which lead to the activation of cPLA2 and 12-LOX. Further analysis of signaling pathways induced by oxidized phospholipids that lead to specific monocyte adhesion should ultimately lead to the development of novel therapeutic approaches against chronic inflammatory diseases.
AB - Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not neutrophils, an initiating event in atherogenesis. Here, we investigate intracellular signaling events induced by oxidized phospholipids in human umbilical vein endothelial cells (HUVECs) that lead to specific monocyte adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn- glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2- oxovaleroyl-sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte adhesion was dependent on protein kinases A and C, extracellular signal-regulated kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic phospholipase A2 (cPLA2). Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids. Peroxisome proliferator-activated receptor α (PPARα) was excluded as a possible target for 12-HETE, because monocyte adhesion was still induced in endothelial cells from PPARα null mice. Together, our results suggest that oxidized phospholipids stimulate HUVECs to specifically bind monocytes involving MAPK pathways, which lead to the activation of cPLA2 and 12-LOX. Further analysis of signaling pathways induced by oxidized phospholipids that lead to specific monocyte adhesion should ultimately lead to the development of novel therapeutic approaches against chronic inflammatory diseases.
KW - 12-lipoxygenase
KW - Atherosclerosis
KW - Cytosolic phospholipase A
KW - Endothelial cells
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U2 - 10.1194/jlr.M500555-JLR200
DO - 10.1194/jlr.M500555-JLR200
M3 - Article
C2 - 16461778
AN - SCOPUS:33646780193
SN - 0022-2275
VL - 47
SP - 1054
EP - 1062
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 5
ER -