| First Author | Hillgruber C | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 1 | Pages | 77-86 |
| PubMed ID | 23812299 | Mgi Jnum | J:205720 |
| Mgi Id | MGI:5546291 | Doi | 10.1038/jid.2013.292 |
| Citation | Hillgruber C, et al. (2014) Blocking von Willebrand factor for treatment of cutaneous inflammation. J Invest Dermatol 134(1):77-86 |
| abstractText | 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 Ibalpha (GPIbalpha)), the VWF/GPIbalpha 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. |
