We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Blocking Von Willebrand Factor for Treatment of Cutaneous Inflammation.
- Authors
Hillgruber, Carina; Steingräber, Annika K.; Pöppelmann, Birgit; Denis, Cécile V.; Ware, Jerry; Vestweber, Dietmar; Nieswandt, Bernhard; Schneider, Stefan W; Goerge, Tobias
- Abstract
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.
- Subjects
VON Willebrand factor; INFLAMMATION treatment; HEMOSTASIS; CONTACT dermatitis; LEUCOCYTES; NEUTROPHILS
- Publication
Journal of Investigative Dermatology, 2014, Vol 134, Issue 1, p77
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1038/jid.2013.292