Calpain activity and expression are increased in splenic inflammatory cells associated with experimental allergic encephalomyelitis

Since calcium-activated neutral proteinase (calpain) activity and expressio n are significantly increased in activated glial/inflammatory cells in the central nervous system of animals with autoimmune demyelinating diseases, t his enzyme may also play a role in peripheral organ systems in these diseas es. In this study, the activity and expression of calpain and the endogenou s inhibitor, calpastatin, were evaluated at transcriptional and translation al levels in spleens of Lewis rats with acute experimental allergic encepha lomyelitis (EAE) prior to the onset of clinical symptoms. Calpain activity and translational expression were increased by 475.5% and 44.3% respectivel y, on day 4 post-induction in adjuvant controls and animals with EAE. These levels remained elevated compared to normal controls on days 8 and 12. Cal pastatin translational expression was similarly increased at these time poi nts although transcriptional expression was not significantly altered at an y time following induction of EAE. Likewise, transcriptional expression of mu-calpain was unchanged following induction, while small increases in m-ca lpain transcriptional expression were observed on days 2 and 8. Most calpai n expression was observed in activated splenic macrophages at day 8 post-in duction even though activated T cells were also calpain positive. In spinal cords of animals with EAE, calpain expression was significantly increased in rats with severe disease compared to those exhibiting only mild symptoms at day 12 post-induction. Thus, prior to symptomatic EAE, increased calpai n activity and expression in peripheral lymphoid organs may play an importa nt role in T cell migration and subsequent disease progression. (C) 1999 El sevier Science B.V. All rights reserved.