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Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia

Author

Listed:
  • Kashyap Krishnasamy

    (Hannover Medical School
    Hannover Medical School)

  • Anne Limbourg

    (Hannover Medical School
    Hannover Medical School
    Hannover Medical School)

  • Tamar Kapanadze

    (Hannover Medical School
    Hannover Medical School
    Hannover Medical School)

  • Jaba Gamrekelashvili

    (Hannover Medical School
    Hannover Medical School)

  • Christian Beger

    (Hannover Medical School
    Hannover Medical School
    Hannover Medical School)

  • Christine Häger

    (Hannover Medical School
    Hannover Medical School)

  • Vladimir J. Lozanovski

    (Hannover Medical School
    University Hospital Heidelberg)

  • Christine S. Falk

    (Hannover Medical School
    Hannover Medical School)

  • L. Christian Napp

    (Hannover Medical School
    Hannover Medical School)

  • Johann Bauersachs

    (Hannover Medical School)

  • Matthias Mack

    (Uniklinikum)

  • Hermann Haller

    (Hannover Medical School)

  • Christian Weber

    (Ludwig-Maximilians-University
    Cardiovascular Research Institute Maastricht (CARIM))

  • Ralf H. Adams

    (Max-Planck-Institute for Molecular Biomedicine, and University of Münster)

  • Florian P. Limbourg

    (Hannover Medical School
    Hannover Medical School)

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.

Suggested Citation

  • Kashyap Krishnasamy & Anne Limbourg & Tamar Kapanadze & Jaba Gamrekelashvili & Christian Beger & Christine Häger & Vladimir J. Lozanovski & Christine S. Falk & L. Christian Napp & Johann Bauersachs & , 2017. "Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00953-2
    DOI: 10.1038/s41467-017-00953-2
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    Cited by:

    1. Susanne Fleig & Tamar Kapanadze & Jeremiah Bernier-Latmani & Julia K. Lill & Tania Wyss & Jaba Gamrekelashvili & Dustin Kijas & Bin Liu & Anne M. Hüsing & Esther Bovay & Adan Chari Jirmo & Stephan Hal, 2022. "Loss of vascular endothelial notch signaling promotes spontaneous formation of tertiary lymphoid structures," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Fangying Zhao & Jiangyong He & Jun Tang & Nianfei Cui & Yanyan Shi & Zhifan Li & Shengnan Liu & Yazhou Wang & Ming Ma & Congjian Zhao & Lingfei Luo & Li Li, 2022. "Brain milieu induces early microglial maturation through the BAX-Notch axis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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