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Am J Physiol Endocrinol Metab (July 30, 2002). doi:10.1152/ajpendo.00240.2002
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Articles in PresS, published online ahead of print July 30, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00240.2002
Submitted on June 3, 2002
Accepted on July 23, 2002

Reactive oxygen species mediate leukocyte-endothelium interactions in prostaglandin F2{alpha}-induced luteolysis in rats

Kazuhiro Minegishi1*, Mamoru Tanaka1, Osamu Nishimura1, Shinji Tanigaki1, Kei Miyakoshi1, Hitoshi Ishimoto1, and Yasunori Yoshimura1

1 Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: minegisi{at}xc.catv.ne.jp.

We investigated the contribution of neutrophils to prostaglandin (PG) F2{alpha}-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 8 of pseudopregnancy, subcutaneous injection of PGF2{alpha} (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 PGF2{alpha}-induced increases in adherent leukocytes and MPO activity. Anti-leukocyte antibody also maintained serum progesterone concentrations. Pretreatment with oxygen free radical scavengers, superoxide dismutase (50000U/kg) and catalase (90000U/kg), also attenuated these PGF2{alpha}-induced alterations. Corpora lutea preloaded with dichlorodihydrofluorescein diacetate succinimidyl ester, a fluorescent indicator for determining intracellular ROS generation, exhibited an increase in fluorescence after PGF2{alpha} treatment. These findings suggest that leukocyte-endothelium interactions mediated by ROS generation are important in PGF2{alpha}-induced luteolysis in rats.




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