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)pyridinium 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 conju gation alone nor the binding of noncytotoxic Th2 clone with target cell was sufficient to provoke the process. Although FM1-43 translocation was obser ved in perforin-mediated cytotoxicity, examinations with several other dyes failed to detect the evidence for membrane damages that may cause influx o f the dye. Moreover, the translocation was also observed in Fas-dependent a poptosis. These data indicate that the translocation precedes the damage of plasma membrane and intracellular organella in the course of apoptotic cel l death and may represent the existence of a membrane trafficking that medi ates the translocation of plasma membrane components in the early onset of apoptotic cell death.