Proangiogenic Tie2+ macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease

Annalisa Capobianco, Antonella Monno, Lucia Cottone, Mary Anna Venneri, Daniela Biziato, Francesca Di Puppo, Stefano Ferrari, Michele De Palma, Angelo A. Manfredi, Patrizia Rovere-Querini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2651-2659
Number of pages9
JournalAmerican Journal of Pathology
Volume179
Issue number5
DOIs
Publication statusPublished - Nov 2011

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Fingerprint Dive into the research topics of 'Proangiogenic Tie2+ macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease'. Together they form a unique fingerprint.

Cite this