A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense

Dennis Wolf, Nathaly Anto-Michel, Hermann Blankenbach, Ansgar Wiedemann, Konrad Buscher, Jan David Hohmann, Bock Lim, Marina Bäuml, Alex Marki, Maximilian Mauler, Daniel Duerschmied, Zhichao Fan, Holger Winkels, Daniel Sidler, Philipp Diehl, Dirk M Zajonc, Ingo Hilgendorf, Peter Stachon, Timoteo Marchini, Florian Willecke, Maximilian Schell, Björn Sommer, Constantin von zur Muhlen, Jochen Reinöhl, Teresa Gerhardt, Edward F. Plow, Valentin Yakubenko, Peter Libby, Christoph Bode, Klaus Ley, Karlheinz Peter () and Andreas Zirlik
Additional contact information
Dennis Wolf: University of Freiburg
Nathaly Anto-Michel: University of Freiburg
Hermann Blankenbach: University of Freiburg
Ansgar Wiedemann: University of Freiburg
Konrad Buscher: La Jolla Institute for Allergy and Immunology
Jan David Hohmann: Baker Heart and Diabetes Institute
Bock Lim: Baker Heart and Diabetes Institute
Marina Bäuml: University of Freiburg
Alex Marki: La Jolla Institute for Allergy and Immunology
Maximilian Mauler: University of Freiburg
Daniel Duerschmied: University of Freiburg
Zhichao Fan: La Jolla Institute for Allergy and Immunology
Holger Winkels: La Jolla Institute for Allergy and Immunology
Daniel Sidler: Inselspital, Bern University Hospital
Philipp Diehl: University of Freiburg
Dirk M Zajonc: La Jolla Institute for Allergy and Immunology
Ingo Hilgendorf: University of Freiburg
Peter Stachon: University of Freiburg
Timoteo Marchini: University of Freiburg
Florian Willecke: University of Freiburg
Maximilian Schell: University of Freiburg
Björn Sommer: Medical Faculty of the University of Erlangen
Constantin von zur Muhlen: University of Freiburg
Jochen Reinöhl: University of Freiburg
Teresa Gerhardt: La Jolla Institute for Allergy and Immunology
Edward F. Plow: Cleveland Clinic
Valentin Yakubenko: Cleveland Clinic
Peter Libby: Harvard Medical School
Christoph Bode: University of Freiburg
Klaus Ley: La Jolla Institute for Allergy and Immunology
Karlheinz Peter: Baker Heart and Diabetes Institute
Andreas Zirlik: University of Freiburg

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-02896-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02896-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-02896-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().