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von Willebrand factor promotes leukocyte extravasation
- Source :
- Blood. 116:4712-4719
- Publication Year :
- 2010
- Publisher :
- American Society of Hematology, 2010.
-
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.
- Subjects :
- Blood Platelets
congenital, hereditary, and neonatal diseases and abnormalities
Neutrophils
Immunology
Leukocyte Rolling
Vascular permeability
Peritonitis
Granulocyte
Biochemistry
Antibodies
Capillary Permeability
Mice
Von Willebrand factor
Cell Movement
hemic and lymphatic diseases
von Willebrand Factor
Leukocytes
medicine
Animals
Neutrophil extravasation
biology
Chemistry
Cell Biology
Hematology
Leukocyte extravasation
Extravasation
Mice, Inbred C57BL
P-Selectin
medicine.anatomical_structure
Platelet Glycoprotein GPIb-IX Complex
Glycoprotein Ib
cardiovascular system
biology.protein
Peritoneum
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....cd93d9cc0ff001f90e8ba4767abdbd44