Macrophage scavenger receptor SR-AI contributes to the clearance of von Willebrand factor
Nikolett Wohner,
Vincent Muczynski,
Amel Mohamadi,
Paulette Legendre,
Valérie Proulle,
Gabriel Aymé,
Olivier D. Christophe,
Peter J. Lenting,
Cécile V. Denis,
Caterina Casari
Affiliations
Nikolett Wohner
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Vincent Muczynski
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Amel Mohamadi
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Paulette Legendre
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Valérie Proulle
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France;Service d’Hématologie Biologique, Centre Hospitalier Universitaire Bicêtre, Assistance Publique-Hôpitaux de Paris, 94276 Le Kremlin-Bicêtre, France
Gabriel Aymé
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Olivier D. Christophe
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Peter J. Lenting
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Cécile V. Denis
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Caterina Casari
Institut National de la Santé et de la Recherche Médicale, UMR_S 1176, Univ. Paris-Sud, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France
Previously, we found that LDL-receptor related protein-1 on macrophages mediated shear stress-dependent clearance of von Willebrand factor. In control experiments, however, we observed that von Willebrand factor also binds to macrophages independently of this receptor under static conditions, suggesting the existence of additional clearance-receptors. In search for such receptors, we focused on the macrophage-specific scavenger-receptor SR-AI. von Willebrand factor displays efficient binding to SR-AI (half-maximum binding 14±5 nM). Binding is calcium-dependent and is inhibited by 72±4% in the combined presence of antibodies against the A1- and D4-domains. Association with SR-AI was confirmed in cell-binding experiments. In addition, binding to bone marrow-derived murine SR-AI-deficient macrophages was strongly reduced compared to binding to wild-type murine macrophages. Following expression via hydrodynamic gene transfer, we determined ratios for von Willebrand factor-propeptide over von Willebrand factor-antigen, a marker of von Willebrand factor clearance. Propeptide/antigen ratios were significantly reduced in SR-AI-deficient mice compared to wild-type mice (0.6±0.2 versus 1.3±0.3; P