A DARPin targeting activated Mac-1 is a novel diagnostic tool and potential anti-inflammatory agent in myocarditis, sepsis and myocardial infarction

Basic Res Cardiol. 2021 Mar 15;116(1):17. doi: 10.1007/s00395-021-00849-9.


The monocyte β2-integrin Mac-1 is crucial for leukocyte-endothelium interaction, rendering it an attractive therapeutic target for acute and chronic inflammation. Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the αM I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry. Homology modelling and docking studies defined distinct interaction sites which were verified by mutagenesis. Intravital microscopy showed reduced leukocyte-endothelium adhesion in mice treated with this DARPin. Using mouse models of sepsis, myocarditis and ischaemia/reperfusion injury, we demonstrate therapeutic anti-inflammatory effects. Finally, the activated Mac-1-specific DARPin is established as a tool to detect monocyte activation in patients receiving extra-corporeal membrane oxygenation, as well as suffering from sepsis and ST-elevation myocardial infarction. The activated Mac-1-specific DARPin F7 binds preferentially to activated monocytes, detects inflammation in critically ill patients, and inhibits monocyte and neutrophil function as an efficient new anti-inflammatory agent.

Keywords: DARPin; ECMO; Inflammation; Myocardial infarction; Myocarditis; Sepsis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Surface Display Techniques
  • Cells, Cultured
  • Designed Ankyrin Repeat Proteins / genetics
  • Designed Ankyrin Repeat Proteins / pharmacology*
  • Disease Models, Animal
  • Epitopes
  • Extracorporeal Membrane Oxygenation
  • Humans
  • Macrophage-1 Antigen / genetics
  • Macrophage-1 Antigen / metabolism*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Molecular Docking Simulation
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocarditis / drug therapy*
  • Myocarditis / immunology
  • Myocarditis / metabolism
  • Myocarditis / physiopathology
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Proof of Concept Study
  • Protein Binding
  • ST Elevation Myocardial Infarction / immunology
  • ST Elevation Myocardial Infarction / metabolism
  • Sepsis / drug therapy*
  • Sepsis / immunology
  • Sepsis / metabolism
  • Sepsis / physiopathology
  • Ventricular Function, Left / drug effects


  • Anti-Inflammatory Agents
  • Designed Ankyrin Repeat Proteins
  • Epitopes
  • Macrophage-1 Antigen