This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kitaya, K. Articles by Honjo, H. Search for Related Content PubMed PubMed Citation Articles by Kitaya, K. Articles by Honjo, H.

Expression of Macrophage Inflammatory Protein-1ß in Human Endometrium: Its Role in Endometrial Recruitment of Natural Killer Cells

Department of Obstetrics and Gynecology (K.K., T.N., T.O., H.K., H.H.) and Department of Pathology and Applied Neurobiology Research Institute (S.F.), Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

Address all correspondence and requests for reprints to: Kotaro Kitaya, M.D., Ph.D., Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-hirokoji-agaru, Kamigyo-Ku, Kyoto, 602-8566, Japan. E-mail: kitaya{at}koto.kpu-m.ac.jp.

Human endometrium is infiltrated by natural killer (NK) cells throughout the menstrual cycle. The number of endometrial NK cells is low in the proliferative phase, but acutely increases after ovulation, and reaches a peak in the late secretory phase, suggesting that endometrium recruits these leukocytes selectively from circulating peripheral blood. We investigated the expression of macrophage inflammatory protein (MIP)-1ß, a potential chemoattractant for NK cells, in the endometrium. RT-PCR and ELISA revealed that MIP-1ß is expressed in the endometrium throughout the menstrual cycle at both the message and protein levels. MIP-1ß expression is stronger in the secretory phase endometrium than in the proliferative phase endometrium. Immunohistochemistry revealed that MIP-1ß is localized in the surface epithelial cells, glandular epithelial cells, and perivascular stromal cells throughout the menstrual cycle. Stromal cells in a wider perivascular area became immunoreactive in the secretory phase. There was a strong correlation between the endometrial MIP-1ß concentration and the number of endometrial NK cells. Progesterone significantly induced MIP-1ß secretion from cultured endometrial stromal cells, whereas 17ß-estradiol had a weak effect. These results suggest that endometrial MIP-1ß may be involved in the recruitment of NK cells from circulating peripheral blood.

Abbreviations: EP, Early proliferative phase; ES, early secretory phase; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; GRO, growth-regulated oncogene; LP, late proliferative phase; LS, late secretory phase; MIP, macrophage inflammatory protein; MP, mid-proliferative phase; MS, mid-secretory phase; NK, natural killer.

This article has been cited by other articles:

				T. F. Mselle, A. L. Howell, M. Ghosh, C. R. Wira, and C. L. Sentman Human Uterine Natural Killer Cells but Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection by Secretion of CXCL12 J. Virol., November 1, 2009; 83(21): 11188 - 11195. [Abstract] [Full Text] [PDF]

				C. G. Peralta, V. K. Han, J. Horrocks, B. A. Croy, and M. J. van den Heuvel CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile cycles J. Leukoc. Biol., October 1, 2008; 84(4): 1065 - 1074. [Abstract] [Full Text] [PDF]

				C. Carlino, H. Stabile, S. Morrone, R. Bulla, A. Soriani, C. Agostinis, F. Bossi, C. Mocci, F. Sarazani, F. Tedesco, et al. Recruitment of circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy Blood, March 15, 2008; 111(6): 3108 - 3115. [Abstract] [Full Text] [PDF]

				D. B. Keskin, D. S. J. Allan, B. Rybalov, M. M. Andzelm, J. N. H. Stern, H. D. Kopcow, L. A. Koopman, and J. L. Strominger TGFbeta promotes conversion of CD16+ peripheral blood NK cells into CD16- NK cells with similarities to decidual NK cells PNAS, February 27, 2007; 104(9): 3378 - 3383. [Abstract] [Full Text] [PDF]

				M. Kallikourdis, K. G. Andersen, K. A. Welch, and A. G. Betz Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus PNAS, January 9, 2007; 104(2): 594 - 599. [Abstract] [Full Text] [PDF]

				J. Francis, R. Rai, N. J. Sebire, S. El-Gaddal, M. S. Fernandes, P. Jindal, A. Lokugamage, L. Regan, and J. J. Brosens Impaired expression of endometrial differentiation markers and complement regulatory proteins in patients with recurrent pregnancy loss associated with antiphospholipid syndrome Mol. Hum. Reprod., July 1, 2006; 12(7): 435 - 442. [Abstract] [Full Text] [PDF]

				N. J. Hannan, R. L. Jones, C. A. White, and L. A. Salamonsen The Chemokines, CX3CL1, CCL14, and CCL4, Promote Human Trophoblast Migration at the Feto-Maternal Interface Biol Reprod, May 1, 2006; 74(5): 896 - 904. [Abstract] [Full Text] [PDF]

				T. Yamaguchi, K. Kitaya, N. Daikoku, T. Yasuo, S. Fushiki, and H. Honjo Potential Selectin L Ligands Involved in Selective Recruitment of Peripheral Blood CD16(-) Natural Killer Cells into Human Endometrium Biol Reprod, January 1, 2006; 74(1): 35 - 40. [Abstract] [Full Text] [PDF]

				E. Dimitriadis, C.A. White, R.L. Jones, and L.A. Salamonsen Cytokines, chemokines and growth factors in endometrium related to implantation Hum. Reprod. Update, November 1, 2005; 11(6): 613 - 630. [Abstract] [Full Text] [PDF]

				J.V. Fahey, T.M Schaefer, J.Y. Channon, and C.R. Wira Secretion of cytokines and chemokines by polarized human epithelial cells from the female reproductive tract Hum. Reprod., June 1, 2005; 20(6): 1439 - 1446. [Abstract] [Full Text] [PDF]

				K. Kitaya, T. Yamaguchi, and H. Honjo Central Role of Interleukin-15 in Postovulatory Recruitment of Peripheral Blood CD16(-) Natural Killer Cells into Human Endometrium J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2932 - 2940. [Abstract] [Full Text] [PDF]

				C. Dosiou and L. C. Giudice Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives Endocr. Rev., February 1, 2005; 26(1): 44 - 62. [Abstract] [Full Text] [PDF]

				C. L. Sentman, S. K. Meadows, C. R. Wira, and M. Eriksson Recruitment of Uterine NK Cells: Induction of CXC Chemokine Ligands 10 and 11 in Human Endometrium by Estradiol and Progesterone J. Immunol., December 1, 2004; 173(11): 6760 - 6766. [Abstract] [Full Text] [PDF]

				G. Zoumpoulidou, M. C. Jones, S. F. de Mattos, J. M. Francis, L. Fusi, Y. S. Lee, M. Christian, R. Varshochi, E. W.-F. Lam, and J. J. Brosens Convergence of Interferon-{gamma} and Progesterone Signaling Pathways in Human Endometrium: Role of PIASy (Protein Inhibitor of Activated Signal Transducer and Activator of Transcription-y) Mol. Endocrinol., August 1, 2004; 18(8): 1988 - 1999. [Abstract] [Full Text] [PDF]

				K. Kitaya, T. Nakayama, N. Daikoku, S. Fushiki, and H. Honjo Spatial and Temporal Expression of Ligands for CXCR3 and CXCR4 in Human Endometrium J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2470 - 2476. [Abstract] [Full Text] [PDF]