TNF-related apoptosis-inducing ligand mediates tumoricidal activity of human monocytes stimulated by Newcastle disease virus.
The Newcastle disease virus (NDV) has antineoplastic and immunostimulatory properties, and it is currently clinically tested in anticancer therapy. However, the tumoricidal mechanisms of NDV tumor therapy are not fully understood. The results presented here demonstrate that NDV-stimulated human monocytes (Mphi) kill various human tumor cell lines and that this tumoricidal activity is mediated by TRAIL. In contrast to soluble TRAIL-R2-Fc, soluble CD95-Fc and TNF-R2-Fc showed only minimal blocking of the antitumor effect. TRAIL expression is induced on human Mphi after stimulation with NDV and UV-inactivated NDV. These results show that TRAIL induction on human Mphi after NDV stimulation is independent from viral replication and that TRAIL mediates the tumoricidal activity of NDV-stimulated human Mphi.
Washburn
Birgit
B
Division of Cellular Immunology, Tumor Immunology Program, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
Weigand
Markus A
MA
Grosse-Wilde
Anne
A
Janke
Markus
M
Stahl
Heiko
H
Rieser
Eva
E
Sprick
Martin R
MR
Schirrmacher
Volker
V
Walczak
Henning
H
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D058851:GPI-Linked Proteins; D006801:Humans; D008024:Ligands; D008262:Macrophage Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009522:Newcastle disease virus / Q000276:immunology* / Q000502:physiology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000502:physiology; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology / Q000821:virology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis / Q000502:physiology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor