| Autor: |
Lizarralde-Iragorri MA; Inserm - INTS - University of Paris, Paris, France., Lefevre SD; Inserm - INTS - University of Paris, Inserm - INTS - University of Paris, Paris, France., Cochet S; Inserm - INTS - University of Paris, Paris, France., El Hoss S; Inserm - INTS - University of Paris, Paris, France., Brousse V; Hôpital Universitaire Necker Enfants Malades, Paris, France., Filipe A; University of Paris, Paris, France., Dussiot M; Institut Imagine, Université Paris Descartes, Hôpital Necker Enfants Malades, Paris, France., Azouzi S; Inserm - INTS - University of Paris, Paris, France., Le Van Kim C; Inserm - INTS - University of Paris, Paris, France., Rodrigues-Lima F; University of Paris, Paris, France., Français O; ESIEE, Univ Gustave Eiffel, Marne-la-Vallee, France., Le Pioufle B; Université Paris-Saclay, ENS Paris-Saclay, Gif sur Yvette, France., Klei T; Dept. of Blood Cell Research, Sanquin Research and Lab Services, Amsterdam, The Netherlands., van Bruggen R; Dept. of Blood Cell Research, Sanquin Research and Lab Services, Amsterdam, The Netherlands., El Nemer W; Inserm - INTS - University of Paris, Paris, France. |
| Abstrakt: |
Vaso-occlusive crises are the hallmark of sickle cell disease (SCD). They are believed to occur in two steps, starting with adhesion of deformable low-dense red blood cells (RBCs), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of the denser RBCs or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBCs are heterogeneous in terms of density, shape, deformability and surface proteins, which accounts for the differences observed in their adhesion and resistance to shear stress. Sickle RBCs exhibit abnormal adhesion to laminin mediated by Lu/BCAM protein at their surface. This adhesion is triggered by Lu/BCAM phosphorylation in reticulocytes but such phosphorylation does not occur in mature dense RBCs despite firm adhesion to laminin. In this study, we investigated the adhesive properties of sickle RBC subpopulations and addressed the molecular mechanism responsible for the increased adhesion of dense RBCs to laminin in the absence of Lu/BCAM phosphorylation. We provide evidence for the implication of oxidative stress in post-translational modifications of Lu/BCAM that impact its distribution and cis-interaction with glycophorin C at the cell surface activating its adhesive function in sickle dense RBCs. |
