Blocking Von Willebrand Factor for Treatment of Cutaneous Inflammation

• Published in: Journal of investigative dermatology Vol. 134; no. 1; pp. 77 - 86
• Main Authors: Hillgruber, Carina, Steingräber, Annika K., Pöppelmann, Birgit, Denis, Cécile V., Ware, Jerry, Vestweber, Dietmar, Nieswandt, Bernhard, Schneider, Stefan W., Goerge, Tobias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2014; Elsevier Limited
• Subjects: Animals; Antibodies, Blocking - immunology; Antibodies, Blocking - pharmacology; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - immunology; Dermatitis, Contact - drug therapy; Dermatitis, Contact - immunology; Disease Models, Animal; Humans; Immune Complex Diseases - drug therapy; Immune Complex Diseases - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Glycoprotein GPIb-IX Complex - immunology; Vasculitis, Leukocytoclastic, Cutaneous - drug therapy; Vasculitis, Leukocytoclastic, Cutaneous - immunology; von Willebrand Factor - antagonists & inhibitors; von Willebrand Factor - genetics; von Willebrand Factor - immunology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2013.292

Von Willebrand factor (VWF), a key player in hemostasis, is increasingly recognized as a proinflammatory protein. Here, we found a massive accumulation of VWF in skin biopsies of patients suffering from immune complex (IC)–mediated vasculitis (ICV). To clarify the impact of VWF on cutaneous inflammation, we induced experimental ICV either in mice treated with VWF-blocking antibodies or in VWF−/− mice. Interference with VWF led to a significant inhibition of the cutaneous inflammatory response. We confirmed the major findings in irritative contact dermatitis, a second model of cutaneous inflammation. In vivo imaging of cutaneous inflammation in the dorsal skinfold chamber revealed unaffected leukocyte rolling on anti-VWF treatment. However, we identified that reduced leukocyte recruitment is accompanied by reduced vascular permeability. Although VWF-mediated neutrophil recruitment to the peritoneum was described to require the VWF receptor on platelets (glycoprotein Ibα (GPIbα)), the VWF/GPIbα axis was dispensable for cutaneous inflammation. As assessed in tail bleeding assays, we could exclude interference of VWF blockade with hemostasis. Of particular importance, anti-VWF treatment was effective both in prophylactic and therapeutic administration. Thus, VWF represents a promising target for the treatment of cutaneous inflammation, e.g., leukocytoclastic vasculitis.