Annexin V delays apoptosis while exerting an external constraint preventing the release of CD4+ and PrPc+ membrane particles in a human T lymphocyte model.
Phosphatidylserine exposure in the exoplasmic leaflet of the plasma membrane is one of the early hallmarks of cells undergoing apoptosis. The shedding of membrane particles carrying Ags testifying to their tissue origin is another characteristic feature. Annexin V, a protein of as yet unknown specific physiologic function, presents a high Ca2+-dependent affinity for phosphatidylserine and forms two-dimensional arrays at the membrane surface. In this study, we report the delaying action of annexin V on apoptosis in the CEM human T cell line expressing CD4 and the normal cellular prion protein (PrPc), two Ags of particular relevance to cell degeneration and with different attachments to the membrane. The effect of annexin V was additive to that of z-Val-Ala-Asp-fluoromethyl ketone, a potent caspase inhibitor. Annexin V significantly reduced the degree of proteolytic activation of caspase-3, and totally blocked the release of CD4+ and PrPc+ membrane particles. z-Val-Ala-Asp-fluoromethyl ketone was a more powerful antagonist of caspase-3 processing, but prevented the shedding of CD4+ vesicles only partially and had no effect on that of PrPc+ ones. These results suggest that an external membrane constraint, such as that exerted by annexin V, has important consequences on the course of programmed cell death and on the dissemination of particular Ags. In vivo, annexin V had a significant protective effect against spleen weight loss in mice treated by an alkylating agent previously shown to induce lymphocyte apoptosis.
Gidon-Jeangirard
C
C
Institut d'Hématologie et d'Immunologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Hugel
B
B
Holl
V
V
Toti
F
F
Laplanche
J L
JL
Meyer
D
D
Freyssinet
J M
JM
D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology*; D000954:Antigens, Surface / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D015704:CD4 Antigens / Q000187:drug effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018621:PrPC Proteins / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects*
D017304:Annexin A5; D000954:Antigens, Surface; D015704:CD4 Antigens; D061945:Caspase Inhibitors; D008565:Membrane Proteins; D018621:PrPC Proteins; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases