Exogenous hydrogen sulfide induces functional inhibition and cell death of cytotoxic lymphocytes subsets.
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.
Mirandola
Prisco
P
Department of Anatomy, Pharmacology & Forensic Medicine, Human Anatomy Section, University of Parma, Ospedale Maggiore, via Gramsci, Parma, Italy.
Gobbi
Giuliana
G
Sponzilli
Ivonne
I
Pambianco
Maurizia
M
Malinverno
Chiara
C
Cacchioli
Antonio
A
De Panfilis
Giuseppe
G
Vitale
Marco
M
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
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