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

Haematologica. 2021 Sep 1;106(9):2478-2488. doi: 10.3324/haematol.2020.261586.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell*
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Erythrocytes / metabolism
  • Humans
  • Laminin* / metabolism
  • Lutheran Blood-Group System / metabolism
  • Oxidative Stress

Substances

  • Cell Adhesion Molecules
  • Laminin
  • Lutheran Blood-Group System

Grant support

Funding: The work was supported by the Institut National de la Santé et de la Recherche Médicale (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 Ministère de l’Enseignement Supérieur et de la Recherche (Ecole Doctorale BioSPC); they received financial support from: Club du Globule Rouge et du Fer and Société Française d’Hématologie.