Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB-c MiceReportar como inadecuado




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This study focused on the unique properties of both the Ldlr knockout defect closely mimicking the human situation and the BALB-c C inbred mouse strain Th-2 slanted immune response. We generated two immunodeficient strains with severe combined B- and T-cell immunodeficiency with or without a complete lack of natural killer cells to revisit the role of adaptive immune responses on atherogenesis. C-Ldlr- Rag1- mice, which show severe combined B- and T-cell immunodeficiency and C-Ldlr- Rag1- Il2rg- mice, which combine the T- and B-cell defect with a complete lack of natural killer cells and inactivation of multiple cytokine signalling pathways were fed an atherogenic Western type diet WTD. Both B6-Ldlr- and C-Ldlr- immunocompetent mice were used as controls. Body weights and serum cholesterol levels of both immunodeficient strains were significantly increased compared to C-Ldlr- controls, except for cholesterol levels of C-Ldlr- Rag1- double mutants after 12 weeks on the WTD. Quantification of the aortic sinus plaque area revealed that both strains of immunodeficient mice developed significantly more atherosclerosis compared to C-Ldlr- controls after 24 weeks on the WTD. Increased atherosclerotic lesion development in C-Ldlr- Rag1- Il2rg- triple mutants was associated with significantly increased numbers of macrophages and significantly decreased numbers of smooth muscle cells compared to both C-Ldlr- wild type and C-Ldlr- Rag1- double mutants pointing to a plaque destabilizing effect of NK cell loss. Collectively, the present study reveals a previously unappreciated complexity with regard to the impact of lymphocytes on lipoprotein metabolism and the role of lymphocyte subsets in plaque composition.



Autor: Fei Cheng , Laura Twardowski , Kurt Reifenberg , Kerstin Winter, Antje Canisius, Eva Pross, Jianglin Fan, Edgar Schmitt, Leonard

Fuente: http://plos.srce.hr/



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