PuSH - Publikationsserver des Helmholtz Zentrums München

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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Thrombospondin-1 ; Cd47 ; Red Blood Cells ; Calcium ; Cation Channels ; Deformability; Integrin-associated Protein; Dependent Inhibition; Cd47; Death; Activation; Responses; Plasma; Health; Microparticles; Expression
ISSN (print) / ISBN 1478-811X
e-ISSN 1478-811X
Zeitschrift Cell Communication and Signaling
Quellenangaben Band: 18, Heft: 1, Seiten: , Artikelnummer: 155 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Projekt DEAL
Canadian government
CBS postdoctoral fellowship
Faculty of Medicine, Umea University
Swedish Research Council
Deutsche Forschungsgemeinschaft