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Bissinger, R.* ; Petkova-Kirova, P.* ; Mykhailova, O.* ; Oldenborg, P.A.* ; Novikova, E.* ; Donkor, D.A.* ; Dietz, T.* ; Bhuyan, A.A.M.* ; Sheffield, W.P.* ; Grau, M.* ; Artunc, F. ; Kaestner, L.* ; Acker, J.P.* ; Qadri, S.M.*

Thrombospondin-1/CD47 signaling modulates transmembrane cation conductance, survival, and deformability of human red blood cells.

Cell Commun. Signal. 18:155 (2020)
Publ. Version/Full Text DOI PMC
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Background: Thrombospondin-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).Methods: Whole-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.Results: Exposure 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).Conclusions: Taken 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Thrombospondin-1 ; Cd47 ; Red Blood Cells ; Calcium ; Cation Channels ; Deformability; Integrin-associated Protein; Dependent Inhibition; Cd47; Death; Activation; Responses; Plasma; Health; Microparticles; Expression
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 1478-811X
e-ISSN 1478-811X
Journal Cell Communication and Signaling
Quellenangaben Volume: 18, Issue: 1, Pages: , Article Number: 155 Supplement: ,
Publisher BioMed Central
Publishing Place Campus, 4 Crinan St, London N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502400-001
Grants Projekt DEAL
Canadian government
CBS postdoctoral fellowship
Faculty of Medicine, Umea University
Swedish Research Council
Deutsche Forschungsgemeinschaft
DOI 10.1186/s12964-020-00651-5
WOS ID WOS:000573585200003
Scopus ID 85091266201
PubMed ID 32948210
Erfassungsdatum 2020-11-10
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