PMID- 16461778
OWN - NLM
STAT- MEDLINE
DCOM- 20060725
LR  - 20210217
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 47
IP  - 5
DP  - 2006 May
TI  - Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids 
      involves activation of cPLA2 and lipoxygenase.
PG  - 1054-62
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 A(2) (cPLA(2)). 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 alpha 
      (PPARalpha) was excluded as a possible target for 12-HETE, because monocyte 
      adhesion was still induced in endothelial cells from PPARalpha null mice. 
      Together, our results suggest that oxidized phospholipids stimulate HUVECs to 
      specifically bind monocytes involving MAPK pathways, which lead to the activation 
      of cPLA(2) 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.
FAU - Huber, Joakim
AU  - Huber J
AD  - Department of Vascular Biology and Thrombosis Research, Medical University of 
      Vienna, Austria.
FAU - Furnkranz, Alexander
AU  - Furnkranz A
FAU - Bochkov, Valery N
AU  - Bochkov VN
FAU - Patricia, Mary K
AU  - Patricia MK
FAU - Lee, Hans
AU  - Lee H
FAU - Hedrick, Catherine C
AU  - Hedrick CC
FAU - Berliner, Judith A
AU  - Berliner JA
FAU - Binder, Bernd R
AU  - Binder BR
FAU - Leitinger, Norbert
AU  - Leitinger N
LA  - eng
GR  - HL-30568/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060205
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Phospholipid Ethers)
RN  - 0 (oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 1.13.11.12 (Lipoxygenase)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/physiology
MH  - Cell Adhesion/drug effects/*physiology
MH  - Cells, Cultured
MH  - Cytosol/enzymology
MH  - Endothelium, Vascular/*cytology
MH  - Enzyme Activation
MH  - Humans
MH  - Lipoxygenase/*metabolism
MH  - MAP Kinase Signaling System/physiology
MH  - Mice
MH  - Monocytes/*physiology
MH  - Phosphatidylcholines/*pharmacology
MH  - Phospholipases A/*metabolism
MH  - Phospholipid Ethers/pharmacology
MH  - Prostaglandin-Endoperoxide Synthases/physiology
MH  - Protein Kinase C/physiology
MH  - Signal Transduction
MH  - p38 Mitogen-Activated Protein Kinases/physiology
EDAT- 2006/02/08 09:00
MHDA- 2006/07/26 09:00
CRDT- 2006/02/08 09:00
PHST- 2006/02/08 09:00 [pubmed]
PHST- 2006/07/26 09:00 [medline]
PHST- 2006/02/08 09:00 [entrez]
AID - S0022-2275(20)33254-5 [pii]
AID - 10.1194/jlr.M500555-JLR200 [doi]
PST - ppublish
SO  - J Lipid Res. 2006 May;47(5):1054-62. doi: 10.1194/jlr.M500555-JLR200. Epub 2006 
      Feb 5.