Phosphatidylserine exposure during apoptosis is a cell-type-specific eventand does not correlate with plasma membrane phospholipid scramblase expression

Phosphatidylserine (PS) exposure on the surface of cells has been considere d a characteristic feature of apoptosis. However, we demonstrate herein tha t externalization of PS occurs in a cell-type-specific, albeit caspase-depe ndent, manner. Moreover, we could find no correlation in six different cell lines between the level of expression of the phospholipid (PL) scramblase and the capacity of these cells to externalize PS during apoptosis. Overexp ression of PL scramblase in Raji cells, which exhibit low constitutive expr ession of this enzyme, by retroviral transduction of PL scramblase or treat ment of the cells with interferon-alpha, failed to confer the capacity to e xpose PS in response to apoptotic stimuli. However, the lack of PS exposure in some cell types was not due to their inability to translocate PS molecu les to the cell surface, since incubation with thiol reactive agents, such as N-ethylmaleimide, disulfiram and diamide, yielded rapid and pronounced P S exposure in all cell lines. These data suggest that plasma membrane PS ex posure is not an obligatory component of the apoptotic phenotype, and that PL scramblase is not the sole determinant of PS externalization in apoptoti c cells when this occurs. (C) 1999 Academic Press.