title: Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection.
abstract: Programmed cell death (apoptosis) of T-lymphocytes observed in human immunodeficiency virus (HIV) infected individuals could be linked to oxidative stress. Therefore, we have investigated whether reactive oxygen species (ROS) induce apoptosis, which might contribute to the cell loss during progression of HIV-1 infection. ROS were generated in peripheral blood mononuclear cells (PBMC) obtained from HIV-1-positive patients and from healthy controls by stimulation with bacteria or by treatment with hypoxanthine/xanthine oxidase, which has been shown to generate ROS without direct involvement of cytokines. A dose-dependent inhibition of ROS formation correlated with the reduction of apoptosis induced by both bacterial and hypoxanthine/xanthine oxidase stimulation, suggesting that ROS generation was responsible for the induction of apoptosis. In addition, hydrogen peroxide (H2O2) rather than superoxide (O2.-) was observed to induce apoptosis. ROS-dependent apoptosis was shown to be independent of cytokines such as tumor necrosis factor-alpha (TNF-alpha). ROS-induced apoptosis was significantly enhanced in HIV-infected subjects even in the very early stages after infection. Moreover, ROS-mediated apoptosis was not restricted to a particular lymphocyte subset. In view of the diminished oxidative resistance of HIV-infected individuals, our results suggest that ROS-mediated apoptosis might contribute to the deletion of lymphocytes and to the pathogenesis of the disease.
authors.affiliation: Department of Immunology, Paul-Ehrlich-Institute, Federal Agency for Sera and Vaccines, Langen, Germany.
authors.forename: T S
authors.initials: TS
authors.lastname: Dobmeyer
authors.forename: S
authors.initials: S
authors.lastname: Findhammer
authors.forename: J M
authors.initials: JM
authors.lastname: Dobmeyer
authors.forename: S A
authors.initials: SA
authors.lastname: Klein
authors.forename: B
authors.initials: B
authors.lastname: Raffel
authors.forename: D
authors.initials: D
authors.lastname: Hoelzer
authors.forename: E B
authors.initials: EB
authors.lastname: Helm
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
authors.forename: R
authors.initials: R
authors.lastname: Rossol
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology*; D015497:HIV-1; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine