Haematologica (Aug 2020)

Oxidative stress activates red cell adhesion to laminin in sickle cell disease

  • Maria Alejandra Lizarralde-Iragorri,
  • Sophie D. Lefevre,
  • Sylvie Cochet,
  • Sara El Hoss,
  • Valentine Brousse,
  • Anne Filipe,
  • Michael Dussiot,
  • Slim Azouzi,
  • Caroline Le Van Kim,
  • Fernando Rodrigues-Lima,
  • Olivier Français,
  • Bruno Le Pioufle,
  • Thomas Klei,
  • Robin van Bruggen,
  • Wassim El Nemer

DOI
https://doi.org/10.3324/haematol.2020.261586
Journal volume & issue
Vol. 106, no. 9

Abstract

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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.