Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein.
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.
Gijbels
K
K
Rega Institute, University of Leuven Medical School, Belgium.
Proost
P
P
Masure
S
S
Carton
H
H
Billiau
A
A
Opdenakker
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001933:Brain Stem / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D017364:Collagenases / Q000134:cerebrospinal fluid*; D004492:Edetic Acid / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology*; D006168:Guinea Pigs; D020780:Matrix Metalloproteinase 9; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000737:chemistry / Q000378:metabolism*; D010618:Phenanthrolines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors
D004676:Myelin Basic Protein; D010618:Phenanthrolines; D011480:Protease Inhibitors; D004492:Edetic Acid; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; C025205:1,10-phenanthroline