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Beta2 integrin-dependent neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes.
- Source :
-
Circulation [Circulation] 2002 Nov 05; Vol. 106 (19), pp. 2434-41. - Publication Year :
- 2002
-
Abstract
- Background: Oxidation of LDL produces a series of biologically active, oxidized lipids. Among them, isoprostanes, and in particular iPF(2alpha)-III, seem to be crucial in mediating some of the key cellular events seen in myocardial ischemia-reperfusion injury.<br />Methods and Results: Minimally modified LDL (MM-LDL) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen. Rapid adhesion triggering correlates with degree of LDL oxidation and accumulation of isoprostanes. Isoprostanes accumulated in MM-LDL are major determinants of the proadhesive effect of oxidized LDL, as shown by experiments of receptor functional deletion. Moreover, evidence is provided of expression on human neutrophils of a biological active isoprostane receptor distinct from the classical thromboxane A2 receptor.<br />Conclusions: These data suggest that isoprostanes are major contributors to the proadhesive effect induced by MM-LDL on neutrophils and provide additional evidence for the involvement of isoprostanes in the pathogenesis of myocardial ischemia/reperfusion injury.
- Subjects :
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology
Blood Platelets cytology
Blood Platelets physiology
Bridged Bicyclo Compounds, Heterocyclic
Cell Adhesion drug effects
Cell Adhesion immunology
Fatty Acids, Unsaturated
Fibrinogen metabolism
GTP-Binding Protein alpha Subunits, Gi-Go drug effects
GTP-Binding Protein alpha Subunits, Gi-Go metabolism
Humans
Hydrazines pharmacology
Intercellular Adhesion Molecule-1 metabolism
Lipoproteins, LDL chemistry
Lipoproteins, LDL radiation effects
Neutrophils cytology
Neutrophils drug effects
Pertussis Toxin pharmacology
Receptors, Thromboxane agonists
Receptors, Thromboxane antagonists & inhibitors
Signal Transduction drug effects
Signal Transduction physiology
Ultraviolet Rays
CD18 Antigens metabolism
F2-Isoprostanes metabolism
Lipoproteins, LDL pharmacology
Neutrophils physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 106
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 12417539
- Full Text :
- https://doi.org/10.1161/01.cir.0000037223.92135.38