Role of tissue plasminogen activator in clinical aggravation of experimental autoimmune encephalomyelitis and its therapeutic potential.

Abstract

Tissue plasminogen activator (tPA), a component of the plasminogen activator (PA) system, is elevated in inflammatory neurological disorders. In the present study, we explored the immunomodulatory activity of tPA in experimental autoimmune encephalomyelitis (EAE). The EAE was treated with two catalytic inactive tPA variant proteins: S(481)A and S(481)A + KHRR(296-299)AAAA. EAE-induced tPA-/- mice presented with markedly more severe disease than wt EAE mice. Further, treatment with tPA variants, demonstrated a significant suppression of disease severity in tPA-/- and wt mice. Immunological evaluation showed that specific T-cell reactivity was markedly reduced in the tPA-/- animals, as indicated by decreased T-cell reactivity and reduction in T-regulatory cells. The current findings indicate that tPA plays a role in the pathogenesis of EAE. Moreover, successful amelioration of EAE was achieved by administration of tPA variant proteins. This might mean that these proteins have potential for the immunomodulation of neuroinflammation.

• Authors: Tehila Mizrachi, Devorah Gur-Wahnon, Abd Al-Roof Higazi, Talma Brenner
• Journal: Cellular immunology (Cell Immunol) Vol. 348 Pg. 104040 (02 2020) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 31955841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Tissue Plasminogen Activator

Topics

• Animals
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology)
• Female
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Tissue Plasminogen Activator (immunology)