β2 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 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 A 2 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. (Circulation. 2002;106:2434-2441.)