Lethal Effect of Recombinant Human Fas Ligand in Mice Pretreated with Propionibacterium acnes

Masato Tanaka, Takashi Suda, Takehiro Yatomi, Norio Nakamura, Shigekazu Nagata

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    Abstract

    Fas ligand (FasL) is a type II membrane protein. Binding of FasL to its receptor, Fas, induces apoptosis. Matrix metalloproteinase cleaves the membrane-bound human FasL to yield the active soluble form. Here, we have produced a large amount of human soluble rFasL using the yeast, Pichia pastoris. The purified rFasL was found to be glycosylated and to exist as a trimer. The rFasL was effective in inducing apoptosis in a Fas-expressing T cell or a fibroblast cell line. The ID50 of rFasL for mouse Fas-expressing T cells was about 0.5 ng/ml. The killing process with rFasL was quick. That is, >80% Fas-expressing mouse cells were killed within 1 h by a saturation concentration of human rFasL. Intravenous administration of 500 μg of human rFasL had a lethal effect in mice. When the mice were pretreated with Propionibacterium acnes, the subsequent injection of 30 μg of human rFasL induced hepatic failure and killed the mice within 24 h. These results indicated that the soluble human FasL is active in inducing apoptosis in vitro and in vivo, and its deleterious effect may be strengthened in patients who are suffering from bacterial infection.

    Original languageEnglish (US)
    Pages (from-to)2303-2309
    Number of pages7
    JournalJournal of Immunology
    Volume158
    Issue number5
    StatePublished - Mar 1 1997

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Tanaka, M., Suda, T., Yatomi, T., Nakamura, N., & Nagata, S. (1997). Lethal Effect of Recombinant Human Fas Ligand in Mice Pretreated with Propionibacterium acnes. Journal of Immunology, 158(5), 2303-2309.