Physiologic regulation of postovulatory neutrophil migration into vagina in mice by a C-X-C chemokine(s).
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 approximately 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.
Sonoda
Y
Y
Department of Molecular Pharmacology, Cancer Research Institute, School of Medicine, Kanazawa University, Ishikawa, Japan.
Mukaida
N
N
Wang
J B
JB
Shimada-Hiratsuka
M
M
Naito
M
M
Kasahara
T
T
Harada
A
A
Inoue
M
M
Matsushima
K
K
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D019743:Chemokines, CXC / Q000502:physiology*; D002630:Chemotactic Factors / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D004971:Estrus / Q000276:immunology; D005260:Female; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D010060:Ovulation / Q000276:immunology*; D011817:Rabbits; D018123:Receptors, Interleukin / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D014621:Vagina / Q000276:immunology*
D015703:Antigens, CD; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A