A Novel Single-Domain Antibody Against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report.

Abstract

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 A1 domain with picomolar affinity. This sdAb avidity was strongly enhanced via dimerization using a triple Ala linker (KB-VWF-006bi). 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-006bi is an sdAb recognizing the A1 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 A1 domain is pertinent to the participation of VWF in the inflammatory response.

DOI: 10.1161/ATVBAHA.117.309319

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Cite this paper

@article{Aym2017ANS, title={A Novel Single-Domain Antibody Against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report.}, author={Gabriel Aym{\'e} and Fr{\'e}d{\'e}ric Adam and Paulette Legendre and Amine Bazaa and Val{\'e}rie Proulle and C{\'e}cile V. Denis and Olivier D. Christophe and Peter J . Lenting}, journal={Arteriosclerosis, thrombosis, and vascular biology}, year={2017}, volume={37 9}, pages={1736-1740} }