Cell Death-Associated Translocation of Plasma Membrane Components Induced by CTL

• Published in: The Journal of immunology (1950) Vol. 164; no. 9; pp. 4641 - 4648
• Main Authors: Kawasaki, Yukishige, Saito, Takako, Shirota-Someya, Yoshiko, Ikegami, Yuko, Komano, Hajime, Lee, Mi-Heon, Froelich, Christopher J, Shinohara, Nobukata, Takayama, Hajime
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-05-2000
• Subjects: Animals; Apoptosis - genetics; Apoptosis - immunology; Caspase 3; Caspases - deficiency; Caspases - genetics; Caspases - metabolism; Cell Line; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Membrane Permeability - genetics; Cell Membrane Permeability - immunology; Cytoplasmic Granules - immunology; Cytoplasmic Granules - metabolism; Cytotoxicity, Immunologic; Fas antigen; fas Receptor - genetics; fas Receptor - physiology; Fluorescent Dyes - metabolism; Intracellular Membranes - immunology; Intracellular Membranes - metabolism; Mice; Mitochondria - immunology; Mitochondria - metabolism; perforin; Permeability; Pyridinium Compounds - metabolism; Quaternary Ammonium Compounds - metabolism; T-Lymphocytes, Cytotoxic - enzymology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.9.4641

In the very early stages of target cell apoptosis induced by CTL, we found that fluorescence of labeling probes of the target plasma membrane, such as N-(3-triethylammoniumpropyl)-4-(p-dibutylaminostyryl)pyridin ium dibromide (FM1-43), was translocated into intracellular membrane structures including nuclear envelope and mitochondria. This translocation was associated with the execution of CTL-mediated killing, because neither the CTL-target conjugation alone nor the binding of noncytotoxic Th2 clone with target cell was sufficient to provoke the process. Although FM1-43 translocation was observed in perforin-mediated cytotoxicity, examinations with several other dyes failed to detect the evidence for membrane damages that may cause influx of the dye. Moreover, the translocation was also observed in Fas-dependent apoptosis. These data indicate that the translocation precedes the damage of plasma membrane and intracellular organella in the course of apoptotic cell death and may represent the existence of a membrane trafficking that mediates the translocation of plasma membrane components in the early onset of apoptotic cell death.