8-Iso-PGF2 alpha induces beta 2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury.
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(2alpha) on very rapid beta(2)-integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF(2alpha) (1 nmol/L to 20 micromol/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-ss(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(2alpha)-triggered neutrophil adhesion. 8-Iso-PGF(2alpha) 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(2alpha) 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.
Fontana
L
L
Department of Biomedical and Surgical Sciences, Section of General Pathology, University of Verona, Verona, Italy. lechi@borgoroma.univr.it
Giagulli
C
C
Minuz
P
P
Lechi
A
A
Laudanna
C
C
D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D015237:Dinoprost / Q000031:analogs & derivatives / Q000502:physiology*; D028441:F2-Isoprostanes; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018821:CD18 Antigens; D028441:F2-Isoprostanes; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost