title: Redox imbalance of red blood cells impacts T lymphocyte homeostasis: implication in carotid atherosclerosis.
abstract: 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.
authors.affiliation: Istituto Superiore di Sanita' - Infectious, Parasitic and Immune-mediated Diseases, Viale Regina Elena 299, Rome 00161, Italy. elisabetta.profumo@iss.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Profumo
authors.forename: Brigitta
authors.initials: B
authors.lastname: Buttari
authors.forename: Linda
authors.initials: L
authors.lastname: Petrone
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Straface
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Gambardella
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietraforte
authors.forename: Igino
authors.initials: I
authors.lastname: Genuini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Capoano
authors.forename: Bruno
authors.initials: B
authors.lastname: Salvati
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002340:Carotid Artery Diseases / Q000097:blood / Q000276:immunology*; D002450:Cell Communication; D002469:Cell Separation; D002478:Cells, Cultured; D019610:Cytoprotection; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007249:Inflammation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species