Published Online
on October 14, 2002

A more recent version of this article appeared on November 5, 2002

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Submitted on July 25, 2002
Accepted on August 20, 2002

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, and 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.

^* To whom correspondence should be addressed. E-mail: luigi.fontana{at}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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