Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid.
A hallmark of viral meningitis is the invasion of monocytes, lymphocytes and, in the initial phase of the disease, neutrophils into the subarachnoidal space. By their degradation of different macromolecular components in the extracellular connective tissue, matrix metalloproteinases (MMPs) may be essential for the breakdown of the vessel wall in the meninges and the choroid plexus. In this study, the occurrence of MMP-1, MMP-2, MMP-3 and MMP-9 and the two tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, was monitored in the cerebrospinal fluid (CSF) from patients with viral meningitis. Of the proteinases, MMP-9 was found in 13 of 39 (33%) patients, but not in controls; the levels being correlated with the neutrophil cell number in CSF. The CSF concentration of TIMP-1 was increased three-fold compared to the control group (median 233 ng/ml; range 9.4-1252.5 ng/ml) and was correlated to the levels of total protein in CSF. Of the other MMPs and TIMPs assayed, MMP-2 and TIMP-2 were constitutively expressed and not upregulated in viral meningitis. High levels of MMP-9 and MMP-2, as measured by ELISA, was associated with high proteolytic activity detected in CSF by zymography. In conclusion, invasion of the leukocytes into the CSF compartment in viral meningitis may involve MMP-9, its proteolytic effect likely being controlled by expression of TIMP-1.
Kolb
S A
SA
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Lahrtz
F
F
Paul
R
R
Leppert
D
D
Nadal
D
D
Pfister
H W
HW
Fontana
A
A
D000293:Adolescent; D002648:Child; D017364:Collagenases / Q000134:cerebrospinal fluid*; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018093:Gelatinases / Q000134:cerebrospinal fluid; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9; D008587:Meningitis, Viral / Q000134:cerebrospinal fluid / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000134:cerebrospinal fluid; D011480:Protease Inhibitors / Q000134:cerebrospinal fluid; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid*
D011480:Protease Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1