A Novel Single-Domain Antibody Against von Willebrand Factor Al Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report

作者：Ayme Gabriel; Adam Frederic; Legendre Paulette; Bazaa Amine; Proulle Valerie; Denis Cecile V^*; Christophe Olivier D; Lenting Peter J

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(9): 1736-1740.

DOI：10.1161/ATVBAHA.117.309319

• dimerization
• hemorrhage
• inflammation
• mice
• von Willebrand factor

Objective-von Willebrand factor (VWF) is crucial to hemostasis, but also plays a role in inflammatory processes. Unfortunately, no proper monoclonal antibodies to study VWF function in mice are currently available. We therefore aimed to generate single-domain antibodies (sdAbs) recognizing murine VWF and blocking its function in vivo.
Approach and Results-Llama-derived sdAbs recognizing both human and murine VWF were isolated via phage display technology. One of them (designated KB-VWF-006) recognized the VWF A 1 domain with picomolar affinity. This sdAb avidity was strongly enhanced via dimerization using a triple Ala linker (KB-VWF-006)). When administered in vivo to wild-type mice, KB-VWF-006bi dose dependently induced bleeding in a tail clip model. In 2 distinct models of inflammation, KB-VWF-006bi efficiently interfered with leukocyte recruitment and vascular leakage.
Conclusions-KB-VWF-006) is an sdAb recognizing the Al domain of human VWF and murine VWF that interferes with VWF-platelet interactions in vivo. By using this sdAb, we now also show that the Al domain is pertinent to the participation of VWF in the inflammatory response.

• 出版日期2017-9