Promyelocytic HL-60 cells induce apoptosis selectively in transformed cells: involvement of myeloperoxidase, nitric oxide and target cell-derived superoxide anions.
Promyelocytic HL-60 cells induced apoptosis selectively in transformed fibroblasts, but not in nontransformed parental cells or in revertants. Apoptosis induction was independent of direct cell-to-cell contact. It depended on the number of effector and target cells, pointing to the role of factors derived from both cell populations. Inhibitor studies allowed the establishment of the following model for intercellular signalling during apoptosis induction: target cell-derived superoxide anions spontaneously dismutate and form hydrogen peroxide. HL-60 effector cells release MPO which converts hydrogen peroxide into hypochlorous acid. Hypochlorous acid then may interact with target-cell-derived superoxide anions to yield apoptosis-inducing hydroxyl radicals. In addition, effector-cell-derived NO reacts with target-cell-derived superoxide anions and forms apoptosis-inducing peroxynitrite. These data explain the selective apoptosis induction in transformed cells by effector cells of the granulocyte lineage.
Paul
K
K
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Bauer
G
G
D000838:Anions; D017209:Apoptosis / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D018922:HL-60 Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D000838:Anions; D013481:Superoxides; D009569:Nitric Oxide; D009195:Peroxidase