Beta2 integrin-dependent neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F2-isoprostanes.
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.


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.
Fontana
Luigi
L
Department of Medicine, University of Verona, Italy. luigi.fontana@univr.it
Giagulli
Cinzia
C
Cominacini
Luciano
L
Pasini
Anna Fratta
AF
Minuz
Pietro
P
Lechi
Alessandro
A
Sala
Angelo
A
Laudanna
Carlo
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018821:CD18 Antigens / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D028441:F2-Isoprostanes / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated; D005340:Fibrinogen / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014466:Ultraviolet Rays
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018821:CD18 Antigens; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008077:Lipoproteins, LDL; D017482:Receptors, Thromboxane; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D005340:Fibrinogen; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go