title: Exogenous hydrogen sulfide induces functional inhibition and cell death of cytotoxic lymphocytes subsets.
abstract: The toxic effects of exogenous hydrogen sulfide on peripheral blood lymphocytes have been investigated in detail. Hydrogen sulfide is now considered as a gasotransmitter with specific functional roles in different cell types, like neurons and vascular smooth muscle. Here we show that exogenous hydrogen sulfide induces a caspase-independent cell death of peripheral blood lymphocytes that depends on their intracellular glutathione levels, with a physiologically relevant subset specificity for CD8+ T cells and NK cells. Although lymphocyte activation does not modify their sensitivity to HS-, after 24 h exposure to hydrogen sulfide surviving lymphocyte subsets show a dramatically decreased proliferation in response to mitogens and a reduced IL-2 production. Overall, our data demonstrate that HS- reduces the cellular cytotoxic response of peripheral blood lymphocytes as well as their production of IL-2, therefore de-activating the major players of local inflammatory responses, adding new basic knowledge to the clinically well known anti-inflammatory effects of sulfur compounds.
authors.affiliation: Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, via Gramsci, Parma, Italy.
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Giuliana
authors.initials: G
authors.lastname: Gobbi
authors.forename: Ivonne
authors.initials: I
authors.lastname: Sponzilli
authors.forename: Maurizia
authors.initials: M
authors.lastname: Pambianco
authors.forename: Chiara
authors.initials: C
authors.lastname: Malinverno
authors.forename: Antonio
authors.initials: A
authors.lastname: Cacchioli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Panfilis
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D019793:Fluorescein / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D019803:Glutathione Disulfide / Q000032:analysis / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology* / Q000633:toxicity; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D013997:Time Factors
chemical_list: D017304:Annexin A5; D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D007376:Interleukin-2; D005978:Glutathione; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein; D019803:Glutathione Disulfide; D006862:Hydrogen Sulfide