Multiple sclerosis: death receptor expression and oligodendrocyte apoptosis in established lesions.
To determine whether TNF and TRAIL death receptors (DR), and decoy receptors (DcR), play a role in oligodendrocyte depletion in the lesions of chronic multiple sclerosis (MS), we investigated the presence and functionality of these molecules on oligodendrocytes in MS and non-MS brain tissue and on human oligodendrocytes in vitro. For this, we performed immunocytochemistry, Western blotting, TUNEL and FACS analysis for the presence of DR and apoptosis in sections of fresh frozen CNS tissue from cases of chronic MS, other neurologic diseases and normals, and in fetal human oligodendrocytes in vitro. The results showed that although oligodendrocytes demonstrated both DR and DcR, particularly in vitro, there was no predilection of the phenomenon for MS and apoptosis of oligodendrocytes, common in cultures after ligation with TRAIL, was negligible in CNS tissue in situ. Thus, death of oligodendrocytes by apoptosis was an infrequent event in all human CNS samples examined. We postulate that while oligodendrocyte apoptosis might prevail during the initial stages of MS, from our findings other mechanisms probably account for their loss in the established lesion and decoy receptors may play a protective role in oligodendrocyte survival.
Cannella
Barbara
B
Department of Pathology, Neurology and Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, United States. cannella@aecom.yu.edu <cannella@aecom.yu.edu>
Gaupp
Stefanie
S
Omari
Kakuri M
KM
Raine
Cedric S
CS
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009836:Oligodendroglia / Q000473:pathology*; D053218:Receptors, Death Domain / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
D015703:Antigens, CD; D005904:Glial Fibrillary Acidic Protein; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases