Monocyte binding to endothelial cells induced by oxidized phospholipids present in minimally oxidized low density lipoprotein is inhibited by a platelet activating factor receptor antagonist.
Our group has previously demonstrated that oxidized phospholipids derived from mildly oxidized low density lipoprotein (MM-LDL) or oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (oxPAPC) increase monocyte-endothelial interactions. There are indications that the effects of these phospholipids are receptor mediated. Oxidized phospholipids have previously been shown to activate cells via the platelet activating factor (PAF) receptor, therefore, we pretreated human aortic endothelial cells (HAECs) with a PAF-receptor antagonist (WEB 2086) prior to treatment with oxPAPC. WEB 2086 inhibited monocyte binding to endothelial cells induced by oxPAPC (200 micrograms/ml) at concentrations from 1 nM to 10 microM, but had no effect on the induction of monocyte binding induced by lipopolysaccharide (LPS). We were able to isolate and identify several active oxidized phospholipids by combined normal phase high performance liquid chromatography (HPLC) and electrospray mass spectrometry (LC/MS). The induction of monocyte binding to HAECs by two of these partially purified phospholipids was totally abolished by the pretreatment of HAECs with WEB 2086 (100 nM). PAF itself, however, when tested at concentrations from 10 nM to 10 microM had no effect on monocyte binding. These results suggest that several of the oxidized phospholipids present in MM-LDL and oxPAPC induce monocyte binding through a receptor which is perhaps distinct from the PAF-receptor, but can be blocked by the PAF-receptor antagonist WEB 2086.
Leitinger
N
N
Department of Medicine, University of California, Los Angeles, USA.
Watson
A D
AD
Faull
K F
KF
Fogelman
A M
AM
Berliner
J A
JA
D001011:Aorta; D001381:Azepines / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D010742:Phospholipid Ethers / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology*
D001381:Azepines; D008077:Lipoproteins, LDL; D010742:Phospholipid Ethers; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C099252:oxidized low density lipoprotein; C039351:platelet activating factor receptor; C052518:WEB 2086; C043051:1-O-hexadecyl-2-arachidonyl-sn-glycero-3-phosphocholine