Differential expression of matrix metalloproteinases in bacterial meningitis.
Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of various inflammatory diseases of the central nervous system. Evidence is accumulating that gelatinase B (MMP-9) might be involved in the pathogenesis of meningitis, but the spectrum of different MMPs involved in the inflammatory reaction of this disease has not been determined. We investigated the temporal and spatial mRNA expression pattern of gelatinase B in experimental meningococcal meningitis in rats. In contrast to controls, increased mRNA levels with peak values 6 h after injection with menigococci were found in brain specimens of the animals. Elevated MMP-9 mRNA expression was accompanied by enhanced proteolytic activity, as demonstrated by gelatin zymography, and positive immunoreactivity. The mRNA expression pattern of six other MMPs was investigated. Collagenase-3 and stromelysin-1 mRNAs were also found to be upregulated. In contrast, mRNA levels for gelatinase A, matrilysin, stromelysin-2 and stromelysin-3 remained unchanged. As evidenced by significantly increased intracranial pressure and by leakage of intravenously injected Evans blue through the blood vessel walls into the brain parenchyma, the animals injected with meningococci revealed signs of blood-brain barrier disruption. Augmented proteolytic activity of MMP-9 could also be demonstrated in CSF samples obtained from patients with bacterial meningitis, underlining the clinical relevance of our experimental findings. Our data indicate that gelatinase B, collagenase-3 and stromelysin-1 are selectively upregulated in bacterial meningitis and thus may contribute to the pathogenesis of this infectious disease of the central nervous system.
Kieseier
B C
BC
Department of Neurology, Karl-Franzens-Universität, Graz, Austria, Department of Neurology, Ludwig-Maximilians-Universität, München, Germany. bc.kieseir@kfunigraz.ac.at
Paul
R
R
Koedel
U
U
Seifert
T
T
Clements
J M
JM
Gearing
A J
AJ
Pfister
H W
HW
Hartung
H P
HP
D000818:Animals; D001812:Blood-Brain Barrier; D002555:Cerebrospinal Fluid / Q000166:cytology; D017364:Collagenases / Q000134:cerebrospinal fluid / Q000235:genetics*; D018093:Gelatinases / Q000134:cerebrospinal fluid / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9; D008585:Meningitis, Meningococcal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008666:Metalloendopeptidases / Q000134:cerebrospinal fluid / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014158:Transcription, Genetic
D012333:RNA, Messenger; D017364:Collagenases; D018093:Gelatinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507083:Mmp13 protein, rat; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9