title: Hypochlorite-modified low-density lipoprotein induces the apoptotic machinery in Jurkat T-cell lines.
abstract: Myeloperoxidase is abundantly present in inflammatory diseases where activation of monocytes/macrophages and T-cell-mediated immune response occurs. The potent oxidant hypochlorous acid (HOCl), generated by the myeloperoxidase-H(2)O(2)-chloride system of activated phagocytes, converts low-density lipoprotein (LDL) into a proinflammatory lipoprotein particle. Here, we investigated the apoptotic effect of HOCl-LDL, an in vivo occurring LDL modification, on human T-cell lymphoblast-like Jurkat cells. Experiments revealed that HOCl-LDL, depending on the oxidant:lipoprotein molar ratio, induces apoptosis via activation of caspase-3, PARP cleavage and accumulation of reactive oxygen species. The absence of Fas-associated protein with death domain or caspase-8 in mutant cells did not prevent HOCl-LDL induced apoptosis. In contrast, overexpression of the anti-apoptotic Bcl-2 protein protects Jurkat cells against HOCl-LDL-induced apoptosis and prevents accumulation of reactive oxygen species. We conclude that HOCl-LDL-mediated apoptosis in Jurkat cells follows predominantly the intrinsic, mitochondrial pathway. Insitu experiments revealed that an antibody raised against HOCl-LDL recognized epitopes that colocalize both with myeloperoxidase and CD3-positive T-cells in human decidual tissue where local stimulation of the immune system occurs. We provide convincing evidence that formation of HOCl-modified (lipo)proteins generated by the myeloperoxidase-H(2)O(2)-chloride system contributes to apoptosis in T-cells.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center for Molecular Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Resch
authors.forename: Michaela
authors.initials: M
authors.lastname: Semlitsch
authors.forename: Astrid
authors.initials: A
authors.lastname: Hammer
authors.forename: Heidrun
authors.initials: H
authors.lastname: Susani-Etzerodt
authors.forename: Henning
authors.initials: H
authors.lastname: Walczak
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sattler
authors.forename: Ernst
authors.initials: E
authors.lastname: Malle
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019169:Jurkat Cells; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D053200:Fas-Associated Death Domain Protein; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D009195:Peroxidase; D053148:Caspase 3