Titel
Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways
Autor*in
Marlene C. Gerner
Division of Biomedical Science, University of Applied Sciences FH Campus Wien
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Abstract
Numerous observations indicate that red blood cells (RBCs) affect T-cell activation and proliferation. We have studied effects of packed RBCs (PRBCs) on T-cell receptor (TCR) signaling and the molecular mechanisms whereby (P)RBCs modulate T-cell activation. In line with previous reports, PRBCs attenuated the expression of T-cell activation markers CD25 and CD69 upon costimulation via CD3/CD28. In addition, T-cell proliferation and cytokine expression were markedly reduced when T-cells were stimulated in the presence of PRBCs. Inhibitory activity of PRBCs required direct cell–cell contact and intact PRBCs. The production of activation-induced cellular reactive oxygen species, which act as second messengers in T-cells, was completely abrogated to levels of unstimulated T-cells in the presence of PRBCs. Phosphorylation of the TCR-related zeta chain and thus proximal TCR signal transduction was unaffected by PRBCs, ruling out mechanisms based on secreted factors and steric interaction restrictions. In large part, downstream signaling events requiring reactive oxygen species for full functionality were affected, as confirmed by an untargeted MS-based phosphoproteomics approach. PRBCs inhibited T-cell activation more efficiently than treatment with 1 mM of the antioxidant N-acetyl cysteine. Taken together, our data imply that inflammation-related radical reactions are modulated by PRBCs. These immunomodulating effects may be responsible for clinical observations associated with transfusion of PRBCs.
Stichwort
T-cellerythrocytereactive oxygen speciesimmunosuppressionredox regulationphosphoproteomics
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Journal of Biological Chemistry
Band
296
ISSN
0021-9258
Erscheinungsdatum
2021
Publication
Elsevier BV
Projekt
Kod / Identifikator
P29654-B30
Erscheinungsdatum
2021
Zugänglichkeit
Rechteangabe
© 2021 The Authors

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