Proangiogenic Tie2(+) macrophages infiltrate human and murine endometriotic lesions and dictate their growth in a mouse model of the disease.
Am J Pathol
; 179(5): 2651-9, 2011 Nov.
Article
en En
| MEDLINE
| ID: mdl-21924227
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_digestive_diseases
Asunto principal:
Enfermedades Peritoneales
/
Neoplasias Uterinas
/
Receptor TIE-2
/
Endometriosis
/
Leiomioma
/
Macrófagos
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Am J Pathol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Italia