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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:55.)
© 2001 American Heart Association, Inc.

Vascular Biology

8-Iso-PGF₂ Induces ß₂-Integrin–Mediated Rapid Adhesion of Human Polymorphonuclear Neutrophils

A Link Between Oxidative Stress and Ischemia/Reperfusion Injury

Luigi Fontana; Cinzia Giagulli; Pietro Minuz; Alessandro Lechi; Carlo Laudanna

From the Department of Biomedical and Surgical Sciences (L.F., P.M., A.L.) and the Department of Pathology, Section of General Pathology (C.G., C.L.), University of Verona, Verona, Italy.

Correspondence to Dr Luigi Fontana, Department of Biomedical and Surgical Sciences, Medicina Interna C, Policlinico GB Rossi, Piazzale LA Scuro, 37134 Verona, Italy. E-mail lechi{at}borgoroma.univr.it

Abstract—F₂-Isoprostanes are generated from a cyclooxygenase-independent oxidative modification of arachidonic acid. They are present in atherosclerotic plaques and are platelet activators as well as potent vasoconstrictors. Polymorphonuclear neutrophils are major players in ischemia/reperfusion injury and in restenosis after PTCA. The effects of 8-isoprostaglandin (PG) F₂ on very rapid ß₂-integrin–dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF₂ (1 nmol/L to 20 µmol/L) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen but not to the endothelial ligand intercellular adhesion molecule-1. Pretreatment with anti–ß₂-integrin subtypes showed activation of CD11b/CD18 and CD11c/CD18. Adhesion triggering was completely prevented by pertussis toxin. SQ29,548, a specific antagonist of thromboxane A2 receptor, also dose-dependently prevented 8-iso-PGF₂–triggered neutrophil adhesion. 8-Iso-PGF₂ did not trigger adhesion in human monocytes and lymphocytes and did not induce neutrophil chemotaxis or activation of the oxygen free-radical–forming enzyme NADPH-oxidase. These data highlight the role of 8-iso-PGF₂ as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA. The effect is transduced via activation of the receptor for thromboxane A2.

Key Words: neutrophils • adhesion • 8-iso-PGF₂ • thromboxane A2 receptor • ß₂-integrins

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