VASP regulates leukocyte infiltration, polarization, and vascular repair after ischemia

  • In ischemic vascular diseases, leukocyte recruitment and polarization are crucial for revascularization and tissue repair. We investigated the role of vasodilator-stimulated phosphoprotein (VASP) in vascular repair. After hindlimb ischemia induction, blood flow recovery, angiogenesis, arteriogenesis, and leukocyte infiltration into ischemic muscles in VASP−/− mice were accelerated. VASP deficiency also elevated the polarization of the macrophages through increased signal transducer and activator of transcription (STAT) signaling, which augmented the release of chemokines, cytokines, and growth factors to promote leukocyte recruitment and vascular repair. Importantly, VASP deletion in bone marrow–derived cells was sufficient to mimic the increased blood flow recovery of global VASP−/− mice. In chemotaxis experiments, VASP−/− neutrophils/monocytes were significantly more responsive to M1-related chemokines than wild-type controls. Mechanistically, VASP formed complexes with the chemokine receptor CCR2 and β-arrestin-2, and CCR2 receptor internalization was significantly reduced in VASP−/− leukocytes. Our data indicate that VASP is a major regulator of leukocyte recruitment and polarization in postischemic revascularization and support a novel role of VASP in chemokine receptor trafficking.

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Author:Hebatullah Laban, Andreas WeigertORCiDGND, Joana Zink, Amro Elgheznawy, Christoph Schürmann, Lea Günther, Randa Abdel Malik, Sabrina Bothur, Susanne WingertGND, Rolf Bremer, Michael A. RiegerORCiDGND, Bernhard BrüneORCiD, Ralf Peter Louis BrandesORCiDGND, Ingrid FlemingORCiD, Peter M. BenzORCiD
URN:urn:nbn:de:hebis:30:3-500494
DOI:https://doi.org/10.1083/jcb.201702048
ISSN:1540-8140
ISSN:0021-9525
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29507126
Parent Title (English):The journal of cell biology
Publisher:Rockefeller Univ. Press
Place of publication:New York, NY
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/03/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/04/23
Tag:Cytoskeleton; Immunology; Physiology
Volume:217
Issue:4
Page Number:17
First Page:1503
Last Page:1519
Note:
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
HeBIS-PPN:451016327
Institutes:Medizin / Medizin
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen