The atheroprotective effect of 17beta-estradiol depends on complex interactions in adaptive immunity.
Am J Pathol
; 167(1): 267-74, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-15972970
ABSTRACT
Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(-/-)) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arteriosclerosis
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Subgrupos de Linfocitos T
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Estradiol
Límite:
Animals
Idioma:
En
Revista:
Am J Pathol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia