Krishnasamy, Kashyap and Limbourg, Anne and Kapanadze, Tamar and Gamrekelashvili, Jaba and Beger, Christian and Haeger, Christine and Lozanovski, Vladimir J. and Falk, Christine S. and Napp, L. Christian and Bauersachs, Johann and Mack, Matthias and Haller, Hermann and Weber, Christian and Adams, Ralf H. and Limbourg, Florian P. (2017) Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia. NATURE COMMUNICATIONS, 8: 952. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate. Conversely, conditional mutant mice lacking Dll1 or Rbpj show proliferation and transient accumulation of inflammatory macrophages, which antagonizes arteriogenesis and tissue repair. Furthermore, the effects of Notch are sufficient to generate mature macrophages from monocytes ex vivo that display a stable anti-inflammatory phenotype when challenged with pro-inflammatory stimuli. Thus, angiocrine Notch signaling fosters macrophage maturation during ischemia.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL-CELLS; POSTNATAL ARTERIOGENESIS; GENE-EXPRESSION; DENDRITIC CELLS; RBP-J; NOTCH; POLARIZATION; ACTIVATION; MONOCYTES; ANGIOGENESIS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Nephrologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 25 Feb 2019 15:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1999 |
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