1. Beta2 integrin-dependent neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes.
- Author
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Fontana L, Giagulli C, Cominacini L, Pasini AF, Minuz P, Lechi A, Sala A, and Laudanna C
- 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
- 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., 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., 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.
- Published
- 2002
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