An Activation-Specific Anti-Mac-1 Designed-Ankyrin-Repeat-Protein Attenuates Colitis in Mice
Istvan Bojti,
Qianqi Wang,
Tibor Bojti,
Felicitas Bojti,
Patrick Malcolm Siegel,
Timo Heidt,
Martin Moser,
Christoph Bode,
Dirk Westermann,
Karlheinz Peter,
Philipp Diehl
Affiliations
Istvan Bojti
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Qianqi Wang
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Tibor Bojti
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Felicitas Bojti
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Patrick Malcolm Siegel
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Timo Heidt
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Martin Moser
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Christoph Bode
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Dirk Westermann
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
Karlheinz Peter
Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
Philipp Diehl
Department of Cardiology and Angiology, University Heart Center Freiburg—Bad Krozingen, Faculty of Medicine, University of Freiburg, Hugstetter Street 55, 79106 Freiburg, Germany
(1) Background: Inflammatory bowel diseases are complex and multifactorial disorders of unknown etiology. The extravasation of activated leukocytes is a critical step in the pathogenesis of these diseases. Leukocyte integrin Mac-1 (αMβ2; CD11b/CD18) is crucial for the extravasation of myeloid cells, and a novel activation-specific anti-Mac-1 Designed Ankyrin Repeat protein (DARPin F7) is a promising therapeutic agent for inflammatory diseases. In its activated conformation, Mac-1 expresses the high-affinity binding site I-domain, which the DARPin F7 selectively targets. In our study, we aimed to explore the therapeutic potential of anti-Mac-1 DARPin F7 in murine dextrane sodium sulfate (DSS)-induced colitis. (2) Methods: C57BL/6J mice received 3% DSS drinking water for five days, followed by normal drinking water for one week. The mice were treated with DARPin F7 or a control substance daily via intraperitoneal injections. Disease activity index (DAI), colon length, myeloperoxidase (MPO) activity measurements, H&E staining, and qRT-PCR were conducted after euthanizing the mice on day 12. (3) Results: Treatment with DARPin F7 resulted in less pronounced colon shortening and significantly lower histological scores. The DARPin F7-treated animals experienced substantially less disease and myeloperoxidase (MPO) activity. Animals that received DARPin F7 treatment suffered less weight loss and recovered from the weight loss more efficiently. Treatment with DARPin F7 also led to significantly reduced mRNA expression of inflammatory cytokines. (4) Conclusion: Anti-Mac-1 treatment markedly reduced disease activity and inflammatory reaction accompanying DSS-induced colitis in mice.
