title: von Willebrand factor promotes leukocyte extravasation.
abstract: von Willebrand factor (VWF) is an important player in hemostasis but has also been suggested to promote inflammatory processes. Gene ablation of VWF causes a simultaneous defect in P-selectin expression making it difficult to identify VWF-specific functions. Therefore, we analyzed whether blocking antibodies against VWF would be able to interfere with neutrophil extravasation. We found that these antibodies inhibited neutrophil recruitment into thioglycollate-inflamed peritoneum and KC-stimulated cremaster by approximately 50%. Whereas platelet-VWF was not involved, the contribution of VWF to granulocyte recruitment was strictly dependent on the presence of platelets and the accessibility of their VWF-receptor glycoprotein Ib. Surprisingly, platelet P-selectin was largely dispensable for leukocyte extravasation, in agreement with our observation that anti-VWF antibodies did not affect leukocyte rolling and adhesion. Searching for possible effects downstream of leukocyte capture, we found that anti-VWF antibodies significantly inhibited thioglycollate-induced vascular permeability. The increase of permeability was independent of circulating granulocytes, showing that it was not a side effect of neutrophil diapedesis. Collectively, our results demonstrate that VWF-associated platelets strongly support neutrophil extravasation at a step downstream of leukocyte docking to the vessel wall. This step could be related to leukocyte diapedesis facilitated by destabilization of the endothelial barrier.
authors: Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors: Björn
authors: B
authors: Petri
authors: Andre
authors: A
authors: Broermann
authors: Hang
authors: H
authors: Li
authors: Alexander G
authors: AG
authors: Khandoga
authors: Alexander
authors: A
authors: Zarbock
authors: Fritz
authors: F
authors: Krombach
authors: Tobias
authors: T
authors: Goerge
authors: Stefan W
authors: SW
authors: Schneider
authors: Claire
authors: C
authors: Jones
authors: Bernhard
authors: B
authors: Nieswandt
authors: Martin K
authors: MK
authors: Wild
authors: Dietmar
authors: D
authors: Vestweber
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology; D002199:Capillary Permeability; D002465:Cell Movement; D007962:Leukocytes / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D019007:P-Selectin / Q000276:immunology; D010537:Peritoneum / Q000276:immunology; D010538:Peritonitis / Q000276:immunology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D014841:von Willebrand Factor / Q000276:immunology*
chemical_list: D000906:Antibodies; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor