Cell death-associated translocation of plasma membrane components induced by CTL.
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.
Kawasaki
Y
Y
Section for Bioimages, Division of Fundamental Research, Project Research Center, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Saito
T
T
Shirota-Someya
Y
Y
Ikegami
Y
Y
Komano
H
H
Lee
M H
MH
Froelich
C J
CJ
Shinohara
N
N
Takayama
H
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000235:genetics / Q000276:immunology*; D003594:Cytoplasmic Granules / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005456:Fluorescent Dyes / Q000378:metabolism; D007425:Intracellular Membranes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D010539:Permeability; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000502:physiology
C073804:FM1 43; D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D019014:fas Receptor; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases