PHYSIOLOGICAL REGULATION OF POSTOVULATORY NEUTROPHIL MIGRATION INTO VAGINA IN MICE BY A C-X-C CHEMOKINE(S)

Leukocytes, particularly neutrophils, infiltrate into female genital o rgans after ovulation in both humans and mice. In mice, a female sexua l cycle consists of 5 phases: proestrus, estrus, metestrus-1, metestru s-2, and diestrus, Ovulation occurs at estrus; at metestrus-2, a large number of neutrophils infiltrate into the vaginal epithelium accompan ied by an increased neutrophil number in vaginal lavage fluid, Concomi tantly, concentrations of a functional IL-8 homologue, murine macropha ge inflammatory protein (MIP)-2, were increased significantly in vagin al lavage fluid at metestrus-2 as compared with other phases. On the c ontrary, MIP-2 was not detected in plasma during the whole course of a sexual cycle, Moreover, immunohistochemical analyses demonstrated tha t MIP-2 protein expression was prominent at the upper layer of the vag inal 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 vag inal epithelium in a sexual cycle-dependent manner. Furthermore, the a dministration of neutralizing anti-IL-8R homologue Abs at proestrus ab rogated leukocyte infiltration into the vagina at metestrus, However, anti-MIP-2 Abs reduced leukocyte influx at metestrus by similar to 50% , Thus, a murine IL-8 homologue, MIP-2, and its related molecules phys iologically regulate neutrophil migration into the vagina in a sexual cycle-dependent manner.