Schwann cell apoptosis in experimental autoimmune neuritis of the Lewis rat and the functional role of tumor necrosis factor-alpha.
Schwann cell (SC) apoptosis may be a critical factor challenging nerve remyelination and regeneration in experimental autoimmune neuritis (EAN) in the Lewis rat. We therefore analyzed the fate of SC during high-dose antigen therapy of adoptive transfer-(AT-) EAN using rhP2 protein. P2 antigen therapy was associated with an increase of tumor necrosis factor (serum levels 1 h after intravenous (i.v.) injection and an augmentation of T-cell apoptosis. Antigen specific therapy had no clear effect on SC apoptosis. The effects on SC apoptosis were determined by morphological criteria or by in situ tailing (IST) followed by immunocytochemical analysis. Secondly, we neutralized TNF-alpha, released in abundance by antigen treatment but only in small concentrations during natural disease course. We found that the addition of a TNF-alpha neutralizing antiserum resulted in a significant decrease in the rate of SC apoptosis in vivo compared to animals treated with control antigen rhP0 or with rhP2 only.
Weishaupt
A
A
Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, Julius-Maximilians Universität Würzburg, Josef-Schneider-Strasse 11, D-97080, Würzburg, Germany. a.weishaupt@mail.uni-wuerzburg.de
Brück
W
W
Hartung
T
T
Toyka
K V
KV
Gold
R
R
D019264:Adoptive Transfer / Q000009:adverse effects / Q000379:methods; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D005260:Female; D020275:Guillain-Barre Syndrome / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D018996:Myelin P2 Protein / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D018996:Myelin P2 Protein; D014409:Tumor Necrosis Factor-alpha