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Matrix Metalloproteinase-9 in Pneumococcal Meningitis: Activation via an Oxidative Pathway
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Matrix Metalloproteinase-9 in Pneumococcal Meningitis: Activation via an Oxidative Pathway
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Journal Article
Matrix Metalloproteinase-9 in Pneumococcal Meningitis: Activation via an Oxidative Pathway
2003
Overview
In experimental bacterial meningitis, matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) contribute to brain damage. MMP-9 increases in cerebrospinal fluid (CSF) during bacterial meningitis and is associated with the brain damage that is a consequence of the disease. This study assesses the origin of MMP-9 in bacterial meningitis and how ROS modulate its activity. Rat brain-slice cultures and rat polymorphonuclear cells (PMNs) that had been challenged with capsule-deficient heat-inactivated Streptococcus pneumoniae R6 (hiR6) released MMP-9. Coincubation with either catalase, with the myeloperoxidase inhibitor azide, or with the hypochlorous acid scavenger methionine almost completely prevented activation, but not the release, of MMP-9, in supernatants of human PMNs stimulated with hiR6. Thus, in bacterial meningitis, both brain-resident cells and invading PMNs may act as sources of MMP-9, and stimulated PMNs may activate MMP-9 via an ROS-dependent pathway. MMP-9 activation by ROS may represent a target for therapeutic intervention in bacterial meningitis
Publisher
The University of Chicago Press,University of Chicago Press,Oxford University Press
Subject
/ Azides
/ Bacteria
/ Biological and medical sciences
/ Enzymes
/ Experimental bacterial diseases and models
/ Humans
/ Matrix Metalloproteinase 9 - cerebrospinal fluid
/ Matrix Metalloproteinase 9 - metabolism
/ Meningitis, Pneumococcal - enzymology
/ Neurons
/ Rats
