The use of protease inhibitors in experimental allergic neuritis

Details

Serval ID
serval:BIB_A79453C659D4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The use of protease inhibitors in experimental allergic neuritis
Journal
Journal of Neuroimmunology
Author(s)
Schabet  M., Whitaker  J. N., Schott  K., Stevens  A., Zurn  A., Buhler  R., Wietholter  H.
ISSN
0165-5728 (Print)
Publication state
Published
Issued date
03/1991
Volume
31
Number
3
Pages
265-72
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S. --- Old month value: Mar
Abstract
In experimental allergic neuritis (EAN) break-down of myelin is attributed to macrophages, which among other factors contain and secrete proteases. In vitro studies have shown that cathepsin D, an acidic aspartyl endopeptidase, and plasmin can degrade myelin proteins. In order to elucidate a potential therapeutic effect of protease inhibitors we treated Lewis rats, immunized with bovine peripheral nervous system myelin, with epsilon-amino-caproic acid (EACA) or pepstatin. EACA or pepstatin was administered twice daily by intraperitoneal injection beginning on day 6 postimmunization or from the onset of disease (on day 12) through day 24. Compared to saline-treated controls, animals treated with either of the inhibitors showed delayed development of clinical signs and electrophysiological abnormalities. Maximal severity and the further course of disease, however, were not different in control and treated groups. Immunohistological evaluation of sciatic nerve specimens on day 24 postimmunization showed equal numbers of cells positive for ED1 (macrophages) and cathepsin D in all animal groups. There was also no difference in the spontaneous proteolytic activity of the sciatic nerve homogenates at pH 2.8, 5.0, and 7.4. Incubation of the homogenates with pepstatin, however, significantly reduced proteolytic activity at pH 2.8 and 5.0, while EACA had no effect at any pH tested. These results imply that treatment to limit the infiltration of cathepsin D-positive cells or to reduce the induction or activity of cathepsin D may provide a therapeutic avenue for treating inflammatory demyelination of the peripheral nervous system.
Keywords
6-Aminocaproic Acid/pharmacology/*therapeutic use Animals Cathepsin D/analysis Encephalomyelitis, Autoimmune, Experimental/etiology Female Neuritis, Autoimmune, Experimental/*drug therapy/etiology/physiopathology Pepstatins/pharmacology/therapeutic use Plasmin/physiology Protease Inhibitors/*therapeutic use Rats Rats, Inbred Lew Sciatic Nerve/enzymology
Pubmed
Web of science
Create date
28/01/2008 8:44
Last modification date
20/08/2019 15:12
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