8-Iso-PGF _2α Induces β ₂ -Integrin–Mediated Rapid Adhesion of Human Polymorphonuclear Neutrophils

Abstract

Abstract-F 2 -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) F 2␣ on very rapid ␤ 2 -integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF 2␣ (1 nmol/L to 20 mol/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-␤ 2 -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-PGF 2␣ -triggered neutrophil adhesion. 8-Iso-PGF 2␣ 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-PGF 2␣ as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA.

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

“…The increased activity of PLA and PAF-AH may promote the release of 8-isoprostanes and neuroprostanes, which was confirmed by the significantly elevated levels of these compounds in the plasma of patients with both forms of psoriasis. That might further lead to the vicious pathophysiological circle because 8-isoprostanes act as signaling molecules activating the CD11b/CD18 and CD11c/CD18 receptors that play a key role in neutrophil activation and migration [ 64 ]. Another relevant pathway involving oxidative metabolism of PUFAs such as arachidonic acid is by cyclooxygenases.…”

Isoprostanes as physiological mediators of transition to newborn life: novel mechanisms regulating patency of the term and preterm ductus arteriosus

“…However, circulating isoprostanes can also act as intracellular signaling molecules and typically exert vaso-constrictive effects in most vascular beds, as well as smooth muscle constriction of the lymphatic, uterine, gastrointestinal, and tracheobronchial systems (19). The vascular effects of isoprostanes also include platelet activation and adhesion of neutrophils and monocytes to the endothelium (20,21). Recent studies show that monocyte adhesion (22) and platelet aggregation (23) contribute to postnatal DA constriction, suggesting a potential role for isoprostanes in the DA closure process.…”

Pathophysiological Alterations of Redox Signaling and Endocannabinoid System in Granulocytes and Plasma of Psoriatic Patients

“…The increased activity of PLA and PAF-AH may promote the release of 8-isoprostanes and neuroprostanes, as was confirmed by the significantly elevated levels of these compounds in the plasma of patients with both forms of psoriasis. That might further lead to the vicious pathophysiological circle because 8-isoprostanes act as signaling molecules activating the CD11b/CD18 and CD11c/CD18 receptors that play a key role in neutrophil activation and migration [64]. Another relevant pathway involving oxidative metabolism of PUFAs, particularly arachidonic acid, is by cyclooxygenases, the activity of which was increased in case of psoriasis.…”