Angiotensin II–Induced Vascular Dysfunction Depends on Interferon-γ–Driven Immune Cell Recruitment and Mutual Activation of Monocytes and NK-Cells

• DOI: 10.1161/atvbaha.113.301437
• Publication Date: 2013-03-22T04:40:20Z
• Authors: Sabine Kossmann; Melanie Schwenk; Michael Hausding; Susanne H. Karbach; Maria I. Schmidgen; Moritz Brandt; Maike Knorr; Hanhan Hu; Swenja Kröller-Schön; Tanja Schönfelder; Stephan Grabbe; Matthias Oelze; Andreas Daiber; Thomas Münzel; Christian Becker; Philip Wenzel
• Keywords: Monocyte

Immune cells contribute to angiotensin II (ATII)-induced vascular dysfunction and inflammation. Interferon-γ (IFN-γ), an inflammatory cytokine exclusively produced by immune cells, seems be involved in ATII-driven cardiovascular injury, but the actions cellular source of IFN-γ remain incompletely understood.IFN-γ(-/-) Tbx21(-/-) mice were partially protected from ATII-induced (1 mg/kg per day ATII, infused subcutaneously miniosmotic pumps) endothelial smooth muscle dysfunction, whereas overexpressing showed constitutive dysfunction. Absence T-box expressed T (T-bet), transcription factor encoded Tbx21, reduced superoxide peroxynitrite formation attenuated expression nicotinamide adenosine dinucleotide phosphate oxidase subunits as well inducible NO synthase, monocyte chemoattractant protein 1, interleukin-12 aortas ATII-infused mice. Compared with controls, IFN-γ(-/-) characterized ATII-mediated recruitment both natural killer (NK)1.1(+) NK-cells major producers CD11b(+)Gr-1(low) secreting monocytes. Selective depletion adoptive transfer experiments identified essential contributors that T-bet(+)lysozyme M(+) myelomonocytic required for NK-cell into tissue local production.We provide first evidence play role In addition, we disclose T-bet-IFN-γ pathway mutual monocyte-NK-cell activation potential therapeutic targets disease.