Expression of a functional Fas death receptor by human foetal motoneurons

• Published in: Neuroscience Vol. 119; no. 2; pp. 377 - 385
• Main Authors: Lautrette, C, Giraud, S, Vermot-Desroches, C, Preud’homme, J.L, Jauberteau, M.O
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2003; Elsevier
• Subjects: Aborted Fetus - physiology; Acetylcholinesterase - metabolism; Ageing, cell death; Apoptosis; Astrocytes - metabolism; Biological and medical sciences; Blotting, Western - methods; Brain - cytology; Brain - metabolism; Carrier Proteins - pharmacology; CASP8 and FADD-Like Apoptosis Regulating Protein; caspase-8; CD95; Cell physiology; Cells, Cultured; Drug Interactions; Fas antigen; Fas ligand; Fas Ligand Protein; fas Receptor - metabolism; Fluorescent Antibody Technique - methods; Fundamental and applied biological sciences. Psychology; Glial Fibrillary Acidic Protein - metabolism; Humans; In Situ Nick-End Labeling - methods; In Vitro Techniques; Intracellular Signaling Peptides and Proteins; Jurkat Cells - drug effects; Jurkat Cells - metabolism; Membrane Glycoproteins - pharmacology; Molecular and cellular biology; Motor Neurons - drug effects; Motor Neurons - metabolism; Neurofilament Proteins - metabolism; neurons; Spinal Cord - cytology; Spinal Cord - metabolism; Time Factors; PBS; Fas ligand; Ab; CD95; caspase-8; ALS; apoptosis; neurons; TNF; GFAP; mAb; FITC; IFN-γ; TUNEL; FasL; NF; FADD; Human; Peptidases; Enzyme; Caspase; Hydrolases; Fetus; Motor neuron; Apoptosis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(03)00034-4

The expression of the apoptosis inducer Fas (CD95/APO-1) surface receptor by human foetal neurons was investigated in vitro and ex vivo. Immunofluorescence studies of brain and spinal cord cells in primary cultures and of cryosections obtained from 9- and 10-week-old human foetuses, respectively, showed that all Fas-expressing cells were motoneurons (5.3 and 4.2% of the neurons in brain or spinal cord cultures, respectively) on the basis of morphology, reactivity with the monoclonal antibody SMI-32, a mostly motoneuronal marker and acetylcholine esterase expression. Fas was undetectable on the other cell types in culture. The ability of Fas to induce apoptosis of cultured cells from both tissues was determined by using the terminal transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) method combined with the same double-staining procedure. Under basal culture conditions, about 9% of cells, all glial fibrillary acidic protein-expressing astrocytes, were apoptotic. After a 48-h incubation with Fas ligand, mean 28.5% of brain motoneurons and 29.4% of spinal motoneurons underwent apoptosis, with an inhibition by Z-IETD-FMK, a caspase-8 inhibitor. Hence, Fas appears to be functional through a caspase-8-dependent pathway in a subpopulation of human foetal motoneurons.