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(Circulation. 2002;106:2434.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

ß₂ Integrin-Dependent Neutrophil Adhesion Induced by Minimally Modified Low-Density Lipoproteins Is Mainly Mediated by F₂-Isoprostanes

Luigi Fontana, MD; Cinzia Giagulli, PhD; Luciano Cominacini, MD; Anna Fratta Pasini, MD; Pietro Minuz, MD; Alessandro Lechi, MD; Angelo Sala, MD; Carlo Laudanna, MD, PhD

From the Departments of Medicine and Public Health (L.F.), Biomedical and Surgical Sciences (L.C., A.F.P., P.M., A.L.), and Pathology, Section of General Pathology (C.G., C.L.), University of Verona, Italy, and the Department of Pharmacological Science, Center for Cardiopulmonary Pharmacology (A.S.), Milan, Italy.

Correspondence to Dr Luigi Fontana, Department of Medicine and Public Health, Section of Pharmacology, Policlinico "G.Rossi," P.le L.A. Scuro, 10, 37134 Verona, Italy (e-mail luigi.fontana{at}univr.it); and reprint requests to Dr Carlo Laudanna, Department of Pathology, Section of General Pathology, Strada le Grazie, 8, 37134 Verona, Italy (e-mail carlo.laudanna@univr.it).

Background— Oxidation of LDL produces a series of biologically active, oxidized lipids. Among them, isoprostanes, and in particular iPF₂-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.

Key Words: leukocytes • lipoproteins • ischemia • reperfusion

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