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© Pierre Lafaye
Astrocytes marqués par des anticorps VHH anti-GFAP. Des anticorps d'alpagas dirigés contre une protéine spécifique des astrocytes, la GFAP (Glial Fibrillary Acidic Protein), ont été obtenus à partir de camélidés immunisés. La partie VHH (partie de l'anticorps qui reconnaît l'antigène) a été exprimée sous forme recombinante chez Escherichia coli.
Publication : Arteriosclerosis, thrombosis, and vascular biology

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Arteriosclerosis, thrombosis, and vascular biology - 01 Sep 2017

Aymé G, Adam F, Legendre P, Bazaa A, Proulle V, Denis CV, Christophe OD, Lenting PJ,

Link to Pubmed [PMID] – 28642239

Link to DOI – 10.1161/ATVBAHA.117.309319

Arterioscler Thromb Vasc Biol 2017 Sep; 37(9): 1736-1740

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.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.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.