von Willebrand factor promotes leukocyte extravasation

Area of Science:

• Immunology
• Hematology
• Vascular Biology

Background:

• Von Willebrand factor (VWF) plays a role in hemostasis and inflammation.
• Gene ablation of VWF complicates the study of its specific functions due to concurrent P-selectin defects.

Purpose of the Study:

• To investigate the specific role of VWF in neutrophil extravasation using blocking antibodies.
• To elucidate the mechanisms by which VWF influences inflammatory cell recruitment and vascular permeability.

Main Methods:

• Utilized blocking antibodies against VWF to assess their impact on neutrophil recruitment in vivo.
• Examined the role of platelet-VWF and glycoprotein Ib (GPIb) in VWF-mediated granulocyte recruitment.
• Assessed the effect of anti-VWF antibodies on leukocyte rolling, adhesion, and vascular permeability.

Main Results:

• Anti-VWF antibodies inhibited neutrophil recruitment by approximately 50% in inflamed peritoneum and cremaster models.
• VWF's contribution to granulocyte recruitment required platelets and their GPIb receptor, but not platelet P-selectin.
• Anti-VWF antibodies significantly inhibited vascular permeability induced by thioglyoglycollate, independent of circulating granulocytes.

Conclusions:

• VWF-associated platelets significantly promote neutrophil extravasation downstream of leukocyte adhesion.
• VWF may facilitate leukocyte diapedesis by destabilizing the endothelial barrier, impacting vascular permeability.