Cerebrospinal fluid plasminogen, plasmin and protease inhibitors in multiple sclerosis

Objective: to study plasma and cerebrospinal fluid (CSF) concentrations of plasminogen, plasmin, plasmin-alpha(2)-antiplasmin (PAP) complex and the pr otease inhibitory capacity in multiple sclerosis (MS) patients. Design: patients diagnosed as having MS were involved in this study. The re ference subjects had lumbar punctures for clinical reasons but were exclusi ve of having either MS or other types of neurological disease. The identiti es of MS and reference samples were unknown to the researcher until laborat ory results were ready. Setting: department of Neurology, Helsinki University Central Hospital, Fin land. Subjects and methods: plasminogen, plasmin, alpha(2)-antiplasmin, PAP compl ex, alpha(2)-macroglobulin and alpha(1)-antitrypsin levels were studied by microplate chromogenic assays, ELISA and zymography in 34 patients with MS and 24 reference subjects. Results. significantly lower mean levels of CSF plasminogen concentrations were observed in MS in comparison with reference subjects (MS: 0.40+/-0.003 %, REF: 0.67+/-0.12%; P<0.01). Higher concentrations of PAP complex were de tected in CSF of MS patients when compared with reference subjects (P<0.05) . Zymography was employed for the qualitative screening of samples for plas min activity. Plasmin activity could not be detected in either plasma or CS F samples in MS or reference samples. There was no significant differences between CSF alpha(2)-antiplasmin, alpha(2)-macroglobulin and alpha(1)-antit rypsin in MS when compared to reference subjects. There were no significant correlation amongst the CSF anti-proteolytic analytes either in MS or refe rence subjects. Finally, plasma plasminogen, PAP complex and inhibitor conc entrations were within reference ranges in MS patients. Conclusions: Lower levels of CSF plasminogen and quantifiable amounts of PA P complex in MS CSF provide further evidence of plasminogen activation in t he studied patients. We previously found highly raised tissue-type plasmino gen activator activity in MS CSF.(4,5) Inability to detect plasmin activity in CSF with the highly sensitive zymography, suggests formation of inactiv e complexes with alpha(2)-antiplasmin. Furthermore, MS CSF has normal serin e protease inhibitory capacity when compared to reference subjects.