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1.
Circ Res ; 119(12): 1286-1295, 2016 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-27707800

RESUMEN

RATIONALE: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. OBJECTIVE: This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. METHODS AND RESULTS: CD4+ and CD8+ T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (TEM) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited TEM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4+ and CD8+ TEM cells. Reducing the number of TEM cells through a depletion recovery procedure, we show that intravenous TEM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. CONCLUSIONS: TEM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.


Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Inmunidad Innata/fisiología , Várices/metabolismo , Trombosis de la Vena/metabolismo , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Transgénicos , Trombosis/inmunología , Trombosis/metabolismo , Várices/inmunología , Trombosis de la Vena/inmunología
2.
Am J Med ; 126(12): 1142.e9-14, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24262729

RESUMEN

BACKGROUND: In women with sporadic recurrent angioedema with an unknown cause who are unresponsive to antihistamines and have normal C1 inhibitor activity and a negative family history of angioedema, it is unclear whether they have idiopathic angioedema or hereditary angioedema with normal C1 inhibitor, and what impact exogenous estrogens have on their angioedema. METHODS: A cohort of 147 women was analyzed for F12 exon 9 mutations and for the influence of oral contraceptives, hormonal replacement therapy, and pregnancy on their angioedema. RESULTS: A total of 142 women had idiopathic angioedema unresponsive to antihistamines. Five women had an F12 mutation and thereby hereditary angioedema with F12 mutations. Among the women with idiopathic angioedema, 63 had never taken estrogens. There was no estrogen impact in 42 women, a moderate impact in 15 women, and a severe impact in 22 women. The type and dose of estrogens did not differ in women with and without an estrogen impact. In 5 women, idiopathic angioedema disappeared after desogestrel use. Among the 5 women with hereditary angioedema with F12 mutations, angioedema symptoms occurred during 4 pregnancies, whereas no symptoms occurred during any of the 58 pregnancies in women with idiopathic angioedema. CONCLUSIONS: Women with recurrent angioedema unresponsive to antihistamines may have idiopathic angioedema or, more rarely, hereditary angioedema with F12 mutations. Both conditions may be provoked or aggravated by exogenous estrogens. In idiopathic angioedema, treatment with progestins may be helpful.


Asunto(s)
Angioedema/genética , Proteína Inhibidora del Complemento C1/genética , Estrógenos/metabolismo , Antagonistas de los Receptores Histamínicos/farmacología , Estudios de Cohortes , Proteína Inhibidora del Complemento C1/metabolismo , Factor XII/genética , Factor XII/metabolismo , Femenino , Humanos , Mutación , Embarazo
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