Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells.
Preformed Fas ligand (FasL) and APO2 ligand (APO2L)/TNF-related apoptosis-inducing ligand (TRAIL) are stored in the cytoplasm of the human Jurkat T cell line and of normal human T cell blasts. The rapid release of these molecules in their bioactive form is involved in activation-induced cell death. In this study, we show by confocal microscopy that FasL and APO2L/TRAIL are mainly localized in lysosomal-like compartments in these cells. We show also by immunoelectron microscopy that FasL and APO2L/TRAIL are stored inside cytoplasmic compartments approximately 500 nm in diameter, with characteristics of multivesicular bodies. Most of these compartments share FasL and APO2L/TRAIL, although exclusive APO2L/TRAIL labeling can be also observed in separate compartments. Upon PHA activation, the mobilization of these compartments toward the plasma membrane is evident, resulting in the secretion of the internal microvesicles loaded with FasL and APO2L/TRAIL. In the case of activation with anti-CD59 mAb, the secretion of microvesicles labeled preferentially with APO2L/TRAIL predominates. These data provide the basis of a new and efficient mechanism for the rapid induction of autocrine or paracrine cell death during immune regulation and could modify the interpretation of the role of FasL and APO2L/TRAIL as effector mechanisms in physiological and pathological situations.
Monleón
I
I
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain.
Martínez-Lorenzo
M J
MJ
Monteagudo
L
L
Lasierra
P
P
Taulés
M
M
Iturralde
M
M
Piñeiro
A
A
Larrad
L
L
Alava
M A
MA
Naval
J
J
Anel
A
A
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers / Q000032:analysis; D018957:CD59 Antigens / Q000276:immunology; D016923:Cell Death; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D010835:Phytohemagglutinins / Q000494:pharmacology; D022142:Secretory Vesicles / Q000737:chemistry* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018957:CD59 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha