Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways
| Autor: | Andrea Bileck, Pierre Raeven, Liesa S. Ziegler, Christopher Gerner, Marlene C. Gerner, David M. Baron, Ernst W. Müllner, Thomas Öhlinger, Ulrich Salzer, Klaus G. Schmetterer, Lukas Janker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte 0301 basic medicine Erythrocytes T-Lymphocytes PRBCs packed red blood cells Lymphocyte Activation Biochemistry T-cell FACS fluorescence-activated cell sorting Phosphorylation CPD cell proliferation dye Cells Cultured FA formic acid chemistry.chemical_classification reactive oxygen species immunosuppression biology Chemistry mTOR mechanistic target of rapamycin TMRE tetramethylrhodamine ethyl ester CD28 phosphoproteomics DCFDA 2′ 7′-dichlorofluorescin diacetate Cell biology H2O2 hydrogen peroxide Second messenger system Signal transduction Signal Transduction Research Article CD3 PBMCs peripheral blood–derived mononuclear cells Immunomodulation redox regulation 03 medical and health sciences ROS reactive oxygen species Antigens CD IL-2 interleukin-2 Humans Lectins C-Type NaN3 sodium azide Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation IC intracellular Reactive oxygen species 030102 biochemistry & molecular biology T-cell receptor Interleukin-2 Receptor alpha Subunit NAC N-acetyl-l-cysteine Cell Biology ACN acetonitrile PE phycoerythrin 030104 developmental biology TCR T-cell receptor Leukocytes Mononuclear RBCs red blood cells biology.protein FCS fetal calf serum erythrocyte |
| Zdroj: | The Journal of Biological Chemistry |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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