TY - JOUR
T1 - Oxidative stress activates red cell adhesion to laminin in sickle cell disease
AU - Lizarralde-Iragorri, Maria Alejandra
AU - Lefevre, Sophie D.
AU - Cochet, Sylvie
AU - Hoss, Sara El
AU - Brousse, Valentine
AU - Filipe, Anne
AU - Dussiot, Michael
AU - Azouzi, Slim
AU - van Kim, Caroline Le
AU - Rodrigues-Lima, Fernando
AU - Français, Olivier
AU - le Pioufle, Bruno
AU - Klei, Thomas
AU - van Bruggen, Robin
AU - Nemer, Wassim El
N1 - Funding Information: The work was supported by the Institut National de la Sant? et de la Recherche M?dicale (INSERM), the Institut National de la Transfusion Sanguine, the Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051, and the Laboratory of Excellence LaSIPS (ANR-10-LABX-0040-Lasips). The labex GR-Ex is funded by the IdEx program ?Investissements d?avenir? of the French National Research Agency, reference ANR-18-IDEX-0001. MALI and SEH were funded by the Minist?re de l?Enseignement Sup?rieur et de la Recherche (Ecole Doctorale BioSPC); they received financial support from: Club du Globule Rouge et du Fer and Soci?t? Fran?aise d?H?matologie. Publisher Copyright: ©2021 Ferrata Storti Foundation
PY - 2021/9/1
Y1 - 2021/9/1
N2 - aso-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 (RBC), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of denser RBC or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBC 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 RBC 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 RBC 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 RBC 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 RBC.
AB - aso-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 (RBC), or other blood cells such as neutrophils, to the wall of post-capillary venules, followed by trapping of denser RBC or leukocytes in the areas of adhesion because of reduced effective lumen-diameter. In SCD, RBC 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 RBC 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 RBC 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 RBC 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 RBC.
UR - http://www.scopus.com/inward/record.url?scp=85114288040&partnerID=8YFLogxK
U2 - https://doi.org/10.3324/haematol.2020.261586
DO - https://doi.org/10.3324/haematol.2020.261586
M3 - Article
C2 - 32855277
SN - 0390-6078
VL - 106
SP - 2478
EP - 2488
JO - Haematologica
JF - Haematologica
IS - 9
ER -