LEUKOCYTE GELATINASE-B CLEAVAGE RELEASES ENCEPHALITOGENS FROM HUMAN MYELIN BASIC-PROTEIN

Gelatinase B, a marker enzyme for chronic inflammatory diseases such as rheumatoid arthritis and multiple sclerosis (MS), was found to cleave human myelin basic protein (MBP). Human MBP was digested with gelatinase B from leukocytes. The MBP peptide fragments were separated by RP-HPLC and the gelatinase B cleavage sites established by aminoterminal sequence analysis. Several novel P1-P1′ cleavage sites for gelatinase B were found. The positions of the cleavage sites in human MBP were such that at least one peptide coincided with a documented major MBP-autoantigen. This study annotates human MBP as a substrate for human gelatinase B, determines novel P1-P′1 cleavage sites and defines one of the metalloproteinases as a possible link in the pathogenesis of demyelinating diseases such as MS. © 1993 Academic Press. All rights reserved.