Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells Journal Articles uri icon

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  • AbstractBackgroundThrombospondin-1 (TSP-1), a Ca2+-binding trimeric glycoprotein secreted by multiple cell types, has been implicated in the pathophysiology of several clinical conditions. Signaling involving TSP-1, through its cognate receptor CD47, orchestrates a wide array of cellular functions including cytoskeletal organization, migration, cell-cell interaction, cell proliferation, autophagy, and apoptosis. In the present study, we investigated the impact of TSP-1/CD47 signaling on Ca2+dynamics, survival, and deformability of human red blood cells (RBCs).MethodsWhole-cell patch-clamp was employed to examine transmembrane cation conductance. RBC intracellular Ca2+levels and multiple indices of RBC cell death were determined using cytofluorometry analysis. RBC morphology and microvesiculation were examined using imaging flow cytometry. RBC deformability was measured using laser-assisted optical rotational cell analyzer.ResultsExposure of RBCs to recombinant human TSP-1 significantly increased RBC intracellular Ca2+levels. As judged by electrophysiology experiments, TSP-1 treatment elicited an amiloride-sensitive inward current alluding to a possible Ca2+influx via non-selective cation channels. Exogenous TSP-1 promoted microparticle shedding as well as enhancing Ca2+- and nitric oxide-mediated RBC cell death. Monoclonal (mouse IgG1) antibody-mediated CD47 ligation using 1F7 recapitulated the cell death-inducing effects of TSP-1. Furthermore, TSP-1 treatment altered RBC cell shape and stiffness (maximum elongation index).ConclusionsTaken together, our data unravel a new role for TSP-1/CD47 signaling in mediating Ca2+influx into RBCs, a mechanism potentially contributing to their dysfunction in a variety of systemic diseases.


  • Bissinger, Rosi
  • Petkova-Kirova, Polina
  • Mykhailova, Olga
  • Oldenborg, Per-Arne
  • Novikova, Elena
  • Donkor, David A
  • Dietz, Thomas
  • Bhuyan, Abdulla Al Mamun
  • Sheffield, William
  • Grau, Marijke
  • Artunc, Ferruh
  • Kaestner, Lars
  • Acker, Jason P
  • Qadri, Syed M

publication date

  • December 2020