Plasma membrane-derived vesicles (PMVs) released from apoptotic Jurkat cells express upregulated surface Fas and induce apoptosis in recipient viable cells (89.45)

Apoptosis, distinct from necrosis, is irreversible programmed cell death. Characterized by membrane blebbing, DNA fragmentation and cell shrinkage it plays an important role in infection. During viral infection, depending on the virus, apoptosis may either be enhanced or inhibited. Apoptosis can be induced by dexamethasone (DEX), cychloheximide (CHX) and H₂O₂ in vitro in various cell types. PMV release from apoptotic cells (isolated by differential centrifugation, expressing surface phosphatidylserine and of 0.2-1μm average diameter) could be inhibited by pretreatment with calpeptin. Such PMVs, which we distinguished from apoptotic bodies and other microvesicle populations, such as exosomes, have increased Fas expression on DEX and CHX- but not H₂O₂-mediated apoptotic Jurkat cells and an increased capacity to induce apoptosis in recipient healthy Jurkat cells, maximally at a 5:1 PMV-cell ratio. This effect, specific to PMVs from apoptotic cells, as opposed to those from viable cells, occurred after 30 min incubation of recipient, viable cells with PMVs and dose-dependently increased up to a maximum after 5h incubation. Inhibitors of caspase and anti-Fas blocking antibodies have been used to elucidate the importance of these factors in PMV transmission of this apoptotic signal. PMV-mediated apoptosis is currently being investigated for its role in in vitro studies of Coxsackie B3 infection in HeLa cells.