TRAIL induces death of human oligodendrocytes isolated from adult brain.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in various tumour cell lines and, recently, also in normal cells. TRAIL interacts with four receptors: two signalling receptors (TRAIL-R1 and TRAIL-R2) and two decoy receptors (TRAIL-R3 and TRAIL-R4). We have shown that both signalling receptors are present on the surface of oligodendrocytes isolated from adult human brain (ahOL), whereas the decoy receptors are expressed at a low level on ahOL. TRAIL induces ahOL apoptosis--as characterized by Annexin V staining prior to propidium iodide cell uptake--under conditions of protein synthesis inhibition. However, pre-treatment of ahOL with interferon gamma (IFNgamma) evoked susceptibility to TRAIL-induced death, which did not require inhibition of protein synthesis. A blocking experiment with monoclonal antibodies directed against TRAIL-R1 and TRAIL-R2 revealed that TRAIL-R1 is mainly involved in TRAIL-induced apoptosis of ahOL. In contrast to ahOL, microglial cells were completely resistant to cell death induced by TRAIL. Microglial cells had high surface expression of the decoy receptor TRAIL-R3, suggesting that resistance of these glial cells to TRAIL-induced death depends on the presence of the protective effect of TRAIL-R3. Stimulation of microglia with TRAIL increased further expression of TRAIL-R3, but it had no effect on the expression of TRAIL receptors by ahOL. This result may implicate TRAIL as an effector-immune molecule in selective ahOL demise in inflammatory/demyelinating conditions.
Matysiak
Mariola
M
Department of Neurology, Medical University of Lodz, Poland.
Jurewicz
Anna
A
Jaskolski
Dariusz
D
Selmaj
Krzysztof
K
D017304:Annexin A5 / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D058851:GPI-Linked Proteins; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology
D017304:Annexin A5; D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; 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; D007371:Interferon-gamma