Specific and Nonspecific Mechanisms in the Autoimmune Breakdown of Myelin roe I van der veen

The effect of myelin basic protein (MBP) of central nervous tissue onthe protease inhibitors, alpha) antitrypsin (aι AT) and alpha;macroglobulm (агМ) wasstudied (л vitro For this purpose. 2 characteristics of the protease inhibitors were used,viz their pattern after isoelectric focusing and their trypsm-binding capacity Bothfeatures of purified a^AT disappeared in the presence of MBP The tests with агМrevealed that the formation and stability of the complex between ajM and proteasewere reducedThe results of this study suggest that MBP causes an increase in proteolytic activityby inactivating protease inhibitors The potential relevance of these results for demveli-nating processes in man and animal is discussed Accepted for publication August 28, 1984 Myelin basic protein (MBP) has been investigat­ed thoroughly because of its encephalitogemcityfollowing inoculation in genetically susceptibleanimals and its presumed role in the immuno-pathology of multiple sclerosis (MS) Most re­search has dealt with the immunological proper­ties of MBP, both cellular and humoral, andrevealed that the former is important in elicitingexpenmental allergic encephalomyelitis (EAE),while the latter is not. According to Hashun &. Sharpe (1), the cellular immunogenicity of MBP is indeed important, but insufficient to account fully for its encephalitogemcity. Therefore, it seemed important to look for mechanisms of MBP complementary to its immunogenicity In­ creased proteolytic activity has been demonstra­ ted in the border zones of plaques (2, 3), in blood (4) and cerebrospinal fluid (CSF) (5) of patients with MS and in central nervous tissue of animals with EAE (6). This proteolytic activity