Reactive oxygen species mediate leukocyte-endothelium interactions in prostaglandin F2α-induced luteolysis in rats

Abstract

We investigated the contribution of neutrophils to prostaglandin (PG)F2α-induced luteolysis and the role of reactive oxygen species (ROS) as potential mediators of neutrophil accumulation in regressing corpora lutea of superovulated rats. On day 8of pseudopregnancy, subcutaneous injection of PGF2α(500 μg) significantly increased rhodamine 6G-labeled leukocyte adhesion in luteal venules, as observed by intravital microscopy. Neutrophil accumulation was confirmed by significantly increased myeloperoxidase (MPO) activity. Pretreatment with anti-leukocyte antibody (CD18-directed monoclonal antibody, WT-3) significantly inhibited the PGF2α-induced increases in adherent leukocytes and MPO activity. Anti-leukocyte antibody also maintained serum progesterone concentrations. Pretreatment with oxygen free radical scavengers, superoxide dismutase (50,000 U/kg) and catalase (90,000 U/kg), also attenuated these PGF2α-induced alterations. Corpora lutea preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescent indicator for determining intracellular ROS generation, exhibited an increase in fluorescence after PGF2αtreatment. These findings suggest that leukocyte-endothelium interactions mediated by ROS generation are important in PGF2α-induced luteolysis in rats.