title: Matrix metalloproteinase-9 in pneumococcal meningitis: activation via an oxidative pathway.
abstract: 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.
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Damian N
authors.initials: DN
authors.lastname: Meli
authors.forename: Stephan
authors.initials: S
authors.lastname: Christen
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008586:Meningitis, Pneumococcal / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D020780:Matrix Metalloproteinase 9