Triggering of T-cell apoptosis by toxin-related ecto-ADP-ribosyltransferase ART2.
Cytotoxicity induced by protein ADP-ribosylation is a common theme of certain bacterial toxins and of the mammalian ectoenzyme ART2. Exposure of T cells to NAD, the substrate for ART2-catalyzed ADP-ribosylation, induces exposure of phosphatidylserine, uptake of propidium iodide, and fragmentation of DNA. ART2-specific antibodies raised by gene gun immunization block NAD-induced apoptosis. ART2 catalyzed ADP-ribosylation of cell membrane proteins induces formation of cytolytic membrane pores by activating the P2X7 purinoceptor. This alternative pathway to T cell apoptosis could be triggered upon the release of NAD from intracellular stores, for example, during inflammatory tissue damage.
Scheuplein
Felix
F
Institute of Immunology, University Hospital, D-20246 Hamburg, Germany.
Adriouch
Sahahil
S
Glowacki
Gustavo
G
Haag
Friedrich
F
Seman
Michel
M
Koch-Nolte
Friedrich
F
D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D058851:GPI-Linked Proteins; D006801:Humans; D007249:Inflammation; D023421:Models, Animal; D009243:NAD / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*
D058851:GPI-Linked Proteins; D009243:NAD; D036002:ADP Ribose Transferases; C449301:ART1 protein, human