title: Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease.
abstract: Endometriosis affects women of reproductive age, causing infertility and pain. Although immune cells are recruited in endometriotic lesions, their role is unclear. Tie2-expressing macrophages (TEMs) have nonredundant functions in promoting angiogenesis and growth of experimental tumors. Here we show that human TEMs infiltrate areas surrounding newly formed endometriotic blood vessels. We set up an ad hoc mouse model in which TEMs, and not Tie2-expressing endothelial cells, are targeted. We transplanted in wild-type recipients bone marrow cells expressing a suicide gene (Herpes simplex virus type 1 thymidine kinase) under the Tie2 promoter/enhancer. TEMs infiltrated endometriotic lesions. TEM depletion by ganciclovir administration arrested the growth of established lesions, without toxicity. Lesion architecture was disrupted, with: i) loss of glandular organization, ii) reduced neovascularization, and iii) activation of caspase 3 in CD31(+) endothelial cells. Thus, TEMs are important for maintaining the viability of newly formed vessels and represent a potential therapeutic target in endometriosis.
authors.affiliation: Autoimmunity and Vascular Inflammation Unit, San Raffaele Scientific Institute, Milan, Italy. capobianco.annalisa@hsr.it
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capobianco
authors.forename: Antonella
authors.initials: A
authors.lastname: Monno
authors.forename: Lucia
authors.initials: L
authors.lastname: Cottone
authors.forename: Mary Anna
authors.initials: MA
authors.lastname: Venneri
authors.forename: Daniela
authors.initials: D
authors.lastname: Biziato
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Puppo
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Michele
authors.initials: M
authors.lastname: De Palma
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D004715:Endometriosis / Q000473:pathology*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007889:Leiomyoma / Q000098:blood supply*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology; D010532:Peritoneal Diseases / Q000473:pathology*; D042787:Receptor, TIE-2 / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000098:blood supply*; D055815:Young Adult
chemical_list: D042787:Receptor, TIE-2; D053148:Caspase 3