Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission.
Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, this protein triggers an apoptotic program involving an increase of mitochondrial membrane potential and participation of the ceramide pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and fission accompanied by an increase and/or redistribution of fission-associated molecules h-Fis and DRP-1. Importantly, these changes are detected in both resting and activated human T cells, suggesting that Gal-1-induced cell death might become an excellent model to analyze the morphogenetic changes of mitochondria during the execution of cell death. This is the first association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway, providing a rational basis for the immunoregulatory properties of Gal-1 in experimental models of chronic inflammation and cancer.
Matarrese
Paola
P
Department of Drug Research and Evaluation, and Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy.
Tinari
Antonella
A
Mormone
Elisabetta
E
Bianco
Germán A
GA
Toscano
Marta A
MA
Ascione
Barbara
B
Rabinovich
Gabriel A
GA
Malorni
Walter
W
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D053181:Caspase 8; D020169:Caspases; D002478:Cells, Cultured; D064550:Death-Associated Protein Kinases; D037483:Galectin 1 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D007425:Intracellular Membranes / Q000473:pathology; D008564:Membrane Potentials; D008565:Membrane Proteins; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D019139:Tumor Escape; D019014:fas Receptor / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C476525:FIS1 protein, human; D037483:Galectin 1; C445499:LGALS1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D019014:fas Receptor; D064550:Death-Associated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases