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

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.

Oxidative stress-induced endothelial cells-derived exosomes accelerate skin flap survival through Lnc NEAT1-mediated promotion of endothelial progenitor cell function

“…However, silencing Lnc NEAT1 in both HUVEC-Exos and H 2 O 2 -HUVEC-Exos did not affect the fluorescence signal intensity around the skin flap relative to that in HUVEC-Exos and H 2 O 2 -HUVEC-Exos, respectively. Previous study has showed that oxidative stress could activate the adhesion of RBCs to laminin by inducing post-translational modification of Lu/BCAM, which altered its distribution on the cell surface, resulting in aggregates with high binding potential to laminin [ 68 ]. Oxidative stress is one of the important pathogenesis of pancreatitis, leading to upregulation of adhesion molecules, which in turn accelerates disease progression [ 69 ].…”

Microfluidic concurrent assessment of red blood cell adhesion and microcapillary occlusion: potential hemorheological biomarkers in sickle cell disease

“…82,83 It is known that young low-density reticulocytes, released from the bone marrow due to hemolytic stress, adhere to LN in SCD primarily through a Lu/BCAM phosphorylation mediated mechanism, 84 not seen in highdensity mature sickle RBCs. 85 Likely, adherent RBCs in our assay are primarily reticulocytes, although sickle mature RBCs can also adhere on LN (previously reported to be 80% to 90% less than reticulocytes). 11 Altogether, these data suggest clinical relevance for the present assay in SCD, in which the OI measures the impact of stiff sickle RBCs on microvascular occlusion, and RBC adhesion measures the potential of sickle reticulocytes and mature RBCs to attach to exposed sub-endothelial-like matrices, as seen in microvascular damage (Fig.…”

Membrane bending and sphingomyelinase-associated, sulfatide-dependent hypoxic adhesion of sickle mature erythrocytes

“…Furthermore, previously it has been shown that adhesion of reticulocytes to LN (isoform-10) is triggered by oxidative stresses through Lu/BCAM phosphorylation in reticulocytes but not in mature erythrocytes. 41 Nevertheless, given that reticulocytes spent much less time in circulation compared to the mature erythrocytes, the differences that we demonstrated between adhesion of mature erythrocytes and reticulocytes can be explained by the mechanisms that are relevant to the oxidative stress. Therefore, further comprehensive studies could be performed to elucidate the scale of the effects of SMase on sickle red blood cell adhesion.…”