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*
Department of Molecular Pharmacology, Cancer Research Institute, and Departments of
Obstetrics and Gynecology and
Hygiene, School of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan;
§
Department of Molecular Preventive Medicine, School of Medicine, University of Tokyo, Tokyo, Japan,
¶
Second Department of Pathology, School of Medicine, Niigata University, Niigata, Japan; and
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Division of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan
Leukocytes, particularly neutrophils, infiltrate into female
genital organs after ovulation in both humans and mice. In mice, a
female sexual cycle consists of 5 phases: proestrus, estrus,
metestrus-1, metestrus-2, and diestrus. Ovulation occurs at estrus; at
metestrus-2, a large number of neutrophils infiltrate into the vaginal
epithelium accompanied by an increased neutrophil number in vaginal
lavage fluid. Concomitantly, concentrations of a functional IL-8
homologue, murine macrophage inflammatory protein (MIP)-2, were
increased significantly in vaginal lavage fluid at metestrus-2 as
compared with other phases. On the contrary, MIP-2 was not detected in
plasma during the whole course of a sexual cycle. Moreover,
immunohistochemical analyses demonstrated that MIP-2 protein expression
was prominent at the upper layer of the vaginal epithelium at
metestrus-2, in contrast to a marginal staining in the vaginal
epithelium at proestrus and estrus. These results suggest that a C-X-C
chemokine, MIP-2, was produced physiologically in the vaginal
epithelium in a sexual cycle-dependent manner. Furthermore, the
administration of neutralizing anti-IL-8R homologue Abs at
proestrus abrogated leukocyte infiltration into the vagina at
metestrus. However, anti-MIP-2 Abs reduced leukocyte influx at
metestrus by 
50%. Thus, a murine IL-8 homologue, MIP-2, and its
related molecules physiologically regulate neutrophil migration into
the vagina in a sexual cycle-dependent manner.
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