Human mast cells induce caspase-independent DNA fragmentation in leukemic T cells.
Mast cells are known to play an important role in inflammation and host defense. Recent evidence suggests that mast cells may also participate in immune surveillance against cancer cells. In this study, we demonstrate that human mast cells are able to trigger apoptosis in Jurkat T leukemia cells. Fragmentation of Jurkat cell DNA was detectable by JAM assay within 4 h of exposure to HMC-1 mast cells or cultured human cord blood-derived mast cells. HMC-1 mast cells that were fixed with paraformaldehyde retained the ability to induce apoptosis in Jurkat cells while cell-free conditioned supernatants from HMC-1 cell cultures failed to elicit DNA fragmentation, suggesting that mast cells mediate anti-tumor activity via a cell-surface molecule. Surprisingly, the apoptosis-inducing activity of HMC-1 mast cells was not mediated by known tumor necrosis factor (TNF) superfamily members (TNF-alpha, Fas ligand, TRAIL, TWEAK), nor did the fragmentation of Jurkat cell DNA by mast cells require the activity of caspase-3, -8, or -9. Collectively, these data indicate that mast cells trigger caspase-independent apoptosis in leukemic cells via a novel cell-surface molecule, and are consistent with a role for mast cells as anti-tumor effector cells.
Gallagher
Sandra J
SJ
Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Marshall
Jean S
JS
Hoskin
David W
DW
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000494:pharmacology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D000074049:Cytokine TWEAK; D053938:DNA Fragmentation; D004273:DNA, Neoplasm; D005312:Fetal Blood; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism / Q000473:pathology; D015458:Leukemia, T-Cell / Q000235:genetics; D008407:Mast Cells / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D015398:Signal Transduction; D013234:Stem Cells; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048069:Tumor Necrosis Factors; D019014:fas Receptor / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D061945:Caspase Inhibitors; D000074049:Cytokine TWEAK; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C109743:TNFSF12 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D020169:Caspases