Differential expression of matrix metalloproteinases in bacterial meningitis

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of vari ous inflammatory diseases of the central nervous system. Evidence is accumu lating that gelatinase B (MMP-9) might be involved in the pathogenesis of m eningitis, but the spectrum of different MMPs involved in the inflammatory reaction of this disease has not been determined. We investigated the tempo ral and spatial mRNA expression pattern of gelatinase B in experimental men ingococcal meningitis in rats. In contrast to controls, increased mRNA leve ls with peak values 6 h after injection with menigococci were found in brai n specimens of the animals. Elevated MMP-9 mRNA expression was accompanied by enhanced proteolytic activity, as demonstrated by gelatin zymography, an d 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, stro melysin-2 and stromelysin-3 remained unchanged. As evidenced by significant ly increased intracranial pressure and by leakage of intravenously injected Evans blue through the blood vessel walls into the brain parenchyma, the a nimals injected with meningococci revealed signs of blood-brain barrier dis ruption. Augmented proteolytic activity of MMP-9 could also be demonstrated in CSF samples obtained from patients with bacterial meningitis, underlini ng the clinical relevance of our experimental findings. Our data indicate t hat gelatinase B, collagenase-3 and stromelysin-1 are selectively upregulat ed in bacterial meningitis and thus may contribute to the pathogenesis of t his infectious disease of the central nervous system.