Immunologic stimulation of mast cells leads to the reversible exposure of phosphatidylserine in the absence of apoptosis

Background: Loss of phospholipid asymmetry represents one of the hallmarks of apoptosis and results in the surface exposure of phosphatidylserine (PS) which can be indirectly monitored by the calcium-dependent binding of anne xin V. Methods and Results: Here, we provide evidence that the IgE-dependen t stimulation of a rat mast cell line, as well as murine and human nontrans formed mast cells, leads to the exposure of PS at the plasma membrane. The appearance of PS was quantitatively related to allergic mediator release. P harmacological agents that prevent stimulus-secretion coupling blocked PS c ell surface exposure and calcium ionophore-induced PS appearance, suggestin g that it is a direct consequence of exocytosis rather than early signaling events initiated by the aggregation of the high-affinity IgE receptor (Fc epsilon RI). The surface exposure of PS in mast cells was reversible even i n the continuous presence of stimulus and was not associated with the appea rance of apoptotic nuclei, demonstrating that it was independent of physiol ogical cell death. Conclusions: In addition to providing a means of monitor ing exocytosis at the single cell level, our results indicate that PS exter nalization in mast cells is not necessarily related to apoptosis but could be an important feature of the degranulation process. Copyright (C) 2000 S. Karger AG, Basel.