Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis

Elisabetta Profumo; Brigitta Buttari; Linda Petrone; Elisabetta Straface; Lucrezia Gambardella; Donatella Pietraforte; Igino Genuini; Raffaele Capoano; Bruno Salvati; Walter Malorni; Rachele Riganò

doi:10.1160/TH11-02-0110

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(06): 1117-1126.
DOI: 10.1160/TH11-02-0110

Platelets and Blood Cells

Schattauer GmbH

Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis

Elisabetta Profumo

¹Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanita, Rome, Italy

,

Brigitta Buttari

¹Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanita, Rome, Italy

,

Linda Petrone

¹Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanita, Rome, Italy

,

Elisabetta Straface

²Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Rome, Italy

,

Lucrezia Gambardella

²Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Rome, Italy

,

Donatella Pietraforte

³Department of Cell Biology and Neurosciences, Istituto Superiore di Sanita, Rome, Italy

,

Igino Genuini

⁴Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, “Sapienza” University, Rome, Italy

,

Raffaele Capoano

⁵Department of Surgical Sciences, “Sapienza” University, Rome, Italy

,

Bruno Salvati

⁵Department of Surgical Sciences, “Sapienza” University, Rome, Italy

,

Walter Malorni

²Department of Drug Research and Evaluation, Istituto Superiore di Sanita, Rome, Italy

⁶San Raffaele Institute, Sulmona, L’Aquila, Italy

,

Rachele Riganò

¹Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanita, Rome, Italy

› Author Affiliations

Abstract

Summary

Oxidative stress and immune/inflammatory responses are key pathogenetic factors of atherosclerotic disease. In this contest, mechanisms that regulate survival and death of immune cells may be relevant. Previous studies have demonstrated that red blood cells (RBCs) are physiologically able to inhibit apoptosis and to promote proliferation of activated T lymphocytes from healthy subjects. The aim of the present study was to evaluate whether RBCs from patients with carotid atherosclerosis maintain their property to modulate T cell homeostasis. Peripheral blood lymphocytes (PBLs) obtained from healthy subjects were activated in vitro by phytohemagglutinin in the presence/absence of RBCs from patients with carotid atherosclerosis or of in vitro oxidised RBCs from healthy subjects. Levels of reactive oxygen species (ROS) and aging markers of RBCs as well as susceptibility to apoptosis of PBLs were evaluated by flow cytometry. PBL proliferation was evaluated by 3H-methyl-thymidine incorporation assay whereas secretion of cytokines, analysed in view of their key role in T cell function, was assessed by ELISA. Levels of ROS and phosphatidyl-serine externalisation, a sign of RBC aging, resulted significantly higher in RBCs from patients than in those from healthy subjects, whereas surface glycophorin A expression and reduced glutathione content did the opposite. Unlike RBCs obtained from healthy subjects, RBCs from patients and in vitro oxidised RBCs did not protect activated T lymphocytes from apoptosis. Hence, RBCs from patients with carotid atherosclerosis, probably due to their oxidative imbalance, impact T cell integrity and function. Our results suggest a new regulatory role for RBCs in atherosclerosis.

Keywords

Carotid atherosclerosis - red blood cells - peripheral blood lymphocytes - apoptosis - oxidative stress - gender

Full Text

References

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