This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Lin, Y.-J. Articles by Wing, L.-Y. C. Search for Related Content PubMed PubMed Citation Articles by Lin, Y.-J. Articles by Wing, L.-Y. C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Endometriosis

Neutrophils and Macrophages Promote Angiogenesis in the Early Stage of Endometriosis in a Mouse Model

Graduate Institute of Basic Medical Sciences (Y.-J.L., L.-Y.C.W.) and Departments of Immunology (H.-Y.L.) and Physiology (L.-Y.C.W.), Medical College, National Cheng Kung University, Tainan 70101, Taiwan; and Department of Physical Therapy (M.-D.L.), Shu-Zen College of Medicine and Management, Kaohsiung 82144, Taiwan

Address all correspondence and requests for reprints to: Lih-Yuh C. Wing, Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan. E-mail: wing{at}mail.ncku.edu.tw.

Substantial evidence suggests that inflammatory cytokines, immune cells, and angiogenesis are important for endometriosis. In this study, we investigated the role of the sequential events in the development of endometriosis in a mouse model. Uterine tissue was transplanted into the peritoneum of ovariectomized mice and then supplemented with estrogen or vehicle. On different days after transplantation, cell proliferation, angiogenesis, and infiltrated immune cells in ectopic tissue were examined using immunochemical staining. Many disintegrated blood vessels but no bromodeoxyuridine-positive cells in ectopic tissue were observed in the estrogen-treated group on posttransplantation d 1 and 2. On d 4–7, bromodeoxyuridine-positive cells were detected in the blood vessels of ectopic tissue, indicating that angiogenesis was initiated in this stage. Angiogenesis also occurred in ectopic tissue in the vehicle-treated group. Profound infiltration of neutrophils in ectopic tissue occurred on d 1–4, when the number of neutrophils and levels of macrophage inflammatory protein (MIP)-1 and MIP-2 chemokines in peritoneal fluids also reached their peak. Peritoneal macrophage numbers did not change, but secretions of TNF, IL-6, MIP-1, and MIP-2 from macrophages isolated on d 2 were higher than on d 0. In vitro studies showed that peritoneal neutrophils and macrophages secreted vascular endothelial growth factor, which was up-regulated by TNF and IL-6. Our results suggest that neutrophils and macrophages may promote angiogenesis in the early stage of endometriosis and that chemokines and cytokines amplify the angiogenic signal for the growth of endometriotic tissue.

This article has been cited by other articles:

				M. Bacci, A. Capobianco, A. Monno, L. Cottone, F. Di Puppo, B. Camisa, M. Mariani, C. Brignole, M. Ponzoni, S. Ferrari, et al. Macrophages Are Alternatively Activated in Patients with Endometriosis and Required for Growth and Vascularization of Lesions in a Mouse Model of Disease Am. J. Pathol., August 1, 2009; 175(2): 547 - 556. [Abstract] [Full Text] [PDF]

				L. V. P. Tran, N. Tokushige, M. Berbic, R. Markham, and I. S. Fraser Macrophages and nerve fibres in peritoneal endometriosis Hum. Reprod., April 1, 2009; 24(4): 835 - 841. [Abstract] [Full Text] [PDF]

				E. Haber, H.D. Danenberg, N. Koroukhov, R. Ron-El, G. Golomb, and M. Schachter Peritoneal macrophage depletion by liposomal bisphosphonate attenuates endometriosis in the rat model Hum. Reprod., February 1, 2009; 24(2): 398 - 407. [Abstract] [Full Text] [PDF]

				N.M. Nowak, O.M. Fischer, T.C. Gust, U. Fuhrmann, U.-F. Habenicht, and A. Schmidt Intraperitoneal inflammation decreases endometriosis in a mouse model Hum. Reprod., November 1, 2008; 23(11): 2466 - 2474. [Abstract] [Full Text] [PDF]

				O. Celik, S. Hascalik, K. Elter, M.E. Tagluk, B. Gurates, and N.E. Aydin Combating endometriosis by blocking proteasome and nuclear factor-{kappa}B pathways Hum. Reprod., November 1, 2008; 23(11): 2458 - 2465. [Abstract] [Full Text] [PDF]

				M. L. Hull, C. R. Escareno, J. M. Godsland, J. R. Doig, C. M. Johnson, S. C. Phillips, S. K. Smith, S. Tavare, C. G. Print, and D. S. Charnock-Jones Endometrial-Peritoneal Interactions during Endometriotic Lesion Establishment Am. J. Pathol., September 1, 2008; 173(3): 700 - 715. [Abstract] [Full Text] [PDF]

				A. Van Langendonckt, J. Donnez, S. Defrere, G. A.J. Dunselman, and P. G. Groothuis Antiangiogenic and vascular-disrupting agents in endometriosis: pitfalls and promises Mol. Hum. Reprod., May 1, 2008; 14(5): 259 - 268. [Abstract] [Full Text] [PDF]

				A. K. Styer, B. T. Sullivan, M. Puder, D. Arsenault, J. C. Petrozza, T. Serikawa, S. Chang, T. Hasan, R. R. Gonzalez, and B. R. Rueda Ablation of Leptin Signaling Disrupts the Establishment, Development, and Maintenance of Endometriosis-Like Lesions in a Murine Model Endocrinology, February 1, 2008; 149(2): 506 - 514. [Abstract] [Full Text] [PDF]

				U. A. Kayisli, M. Berkkanoglu, Lufang Zhang, G. Kizilay, and A. Arici The Broad-Spectrum Chemokine Inhibitor NR58-3.14.3 Suppresses the Implantation and Survival of Human Endometrial Implants in the Nude Mice Endometriosis Model Reproductive Sciences, December 1, 2007; 14(8): 825 - 835. [Abstract] [PDF]