title: T cell activation induces CuZn superoxide dismutase (SOD)-1 intracellular re-localization, production and secretion.
abstract: Reactive oxygen species (ROS) behave as second messengers in signal transduction for a series of receptor/ligand interactions. A major regulatory role is played by hydrogen peroxide (H2O2), more stable and able to freely diffuse through cell membranes. Copper-zinc superoxide dismutase (CuZn-SOD)-1 is a cytosolic enzyme involved in scavenging oxygen radicals to H2O2 and molecular oxygen, thus representing a major cytosolic source of peroxides. Previous studies suggested that superoxide anion and H2O2 generation are involved in T cell receptor (TCR)-dependent signaling. Here, we describe that antigen-dependent activation of human T lymphocytes significantly increased extracellular SOD-1 levels in lymphocyte cultures. This effect was accompanied by the synthesis of SOD-1-specific mRNA and by the induction of microvesicle SOD-1 secretion. It is of note that SOD-1 increased its concentration specifically in T cell population, while no significant changes were observed in the "non-T" cell counterpart. Moreover, confocal microscopy showed that antigen-dependent activation was able to modify SOD-1 intracellular localization in T cells. Indeed, was observed a clear SOD-1 recruitment by TCR clusters. The ROS scavenger N-acetylcysteine (NAC) inhibited this phenomenon. Further studies are needed to define whether SOD-1-dependent superoxide/peroxide balance is relevant for regulation of T cell activation, as well as in the functional cross talk between immune effectors.
authors.affiliation: Dipartimento di Scienze, Università della Basilicata, 85100 Potenza, Italy; Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Terrazzano
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rubino
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Damiano
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sasso
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Petrozziello
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ucci
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palatucci
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Giovazzino
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Santillo
authors.affiliation: Dipartimento di Scienze e Tecnologie Ambientali Biologiche e Farmaceutiche, II Università di Napoli, 81100 Caserta, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: De Felice
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", 80131 Napoli, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Garbi
authors.affiliation: Medicina Clinica e Chirurgia, Università di Napoli "Federico II", 80131 Napoli, Italy. Electronic address: mondola@unina.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Mondola
authors.affiliation: Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II", 80131 Napoli, Italy. Electronic address: giruggie@unina.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Ruggiero
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D016000:Cluster Analysis; D022162:Cytoplasmic Vesicles / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology*; D008213:Lymphocyte Activation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*
chemical_list: D017252:CD3 Complex; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; C000606290:SOD1 protein, human; D020126:Brefeldin A; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000111:Acetylcysteine
keywords: Human T lymphocyte; Intracellular localization; Microvesicle secretion; SOD-1; T cell activation; TCR triggering