Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils
| Autor: | Devendra K. Vora, Ganesamoorthy Subbanagounder, Cristina Rizza, Gabor Tigyi, Laura J. Pinderski Oslund, Norbert Leitinger, Hans Lee, Mary C. Territo, Peggy T. Shih, Timothy R. Tyner, Nigel Mackman, Judith A. Berliner |
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| Rok vydání: | 1999 |
| Předmět: |
Cell Survival
Neutrophils Vascular Cell Adhesion Molecule-1 Transfection Models Biological Monocytes chemistry.chemical_compound E-selectin medicine Cell Adhesion Cyclic AMP Humans RNA Messenger Cell adhesion Receptor Aorta Cells Cultured Phospholipids Multidisciplinary biology Dose-Response Relationship Drug Cell adhesion molecule Kinase Monocyte Phospholipid Ethers Biological Sciences Cyclic AMP-Dependent Protein Kinases Cell biology Fibronectins Up-Regulation medicine.anatomical_structure chemistry Low-density lipoprotein biology.protein lipids (amino acids peptides and proteins) Endothelium Vascular E-Selectin |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 96(21) |
| ISSN: | 0027-8424 |
| Popis: | We previously have demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC), a component of minimally modified low density lipoprotein (MM-LDL), activates endothelial cells to bind monocytes. 1-Palmitoyl-2- (5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC) and 1- palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine (PGPC), which are present in OxPAPC, MM-LDL, and atherosclerotic lesions, were shown to have a major role in the activation of endothelial cells. We now demonstrate that these two highly similar molecules have dramatically different effects on leukocyte endothelial interactions. POVPC is a potent regulator of monocyte-specific endothelial interactions. Treatment of endothelial cells with POVPC increased monocyte binding by inducing the surface expression of the connecting segment 1 domain of fibronectin; no increase in neutrophil binding was observed. In addition, POVPC strongly inhibited lipopolysaccharide-mediated induction of neutrophil binding and expression of E-selectin protein and mRNA. This inhibition was mediated by a protein kinase A-dependent pathway, resulting in down-regulation of NF-κB-dependent transcription. In contrast, PGPC induced both monocyte and neutrophil binding and expression of E-selectin and vascular cell adhesion molecule 1. We present evidence to suggest that the two phospholipids act by different novel receptors present inXenopuslaevis oocytes and that POVPC, but not PGPC, stimulates a cAMP-mediated pathway. At concentrations equal to that present in MM-LDL, the effect of POVPC dominates and inhibits PGPC-induced neutrophil binding and E-selectin expression in endothelial cells. In summary, our data provide evidence that both POVPC and PGPC are important regulators of leukocyte-endothelial interactions and that POVPC may play a dominant role in a number of chronic inflammatory processes where oxidized phospholipids are known to be present. |
| Databáze: | OpenAIRE |
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