GELATINASE-B IS PRESENT IN THE CEREBROSPINAL-FLUID DURING EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AND CLEAVES MYELIN BASIC-PROTEIN

被引:175
作者
GIJBELS, K
PROOST, P
MASURE, S
CARTON, H
BILLIAU, A
OPDENAKKER, G
机构
[1] USA, SCH MED, REGA INST, FT RUCKER, AL 36360 USA
[2] CATHOLIC UNIV LEUVEN, SCH MED, DEPT BRAIN & BEHAV RES, B-3000 LOUVAIN, BELGIUM
关键词
GELATINASE ACTIVITY; DEMYELINATION; MULTIPLE SCLEROSIS;
D O I
10.1002/jnr.490360409
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Gelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non-induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood-brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders. (C) 1993 Wiley-Liss, Inc.
引用
收藏
页码:432 / 440
页数:9
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