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Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children.
Neuropathol Appl Neurobiol. 2006 Jun; 32(3):304-17.NA

Abstract

We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis.

Authors+Show Affiliations

Clinical Neuroimmunology Laboratory, Department of Research and Neurology, University Hospital of Basel, Basel, Switzerland. Raija.lindberg@unibas.chNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16640649

Citation

Lindberg, R L P., et al. "Gelatinase B [matrix Metalloproteinase (MMP)-9] and Collagenases (MMP-8/-13) Are Upregulated in Cerebrospinal Fluid During Aseptic and Bacterial Meningitis in Children." Neuropathology and Applied Neurobiology, vol. 32, no. 3, 2006, pp. 304-17.
Lindberg RL, Sorsa T, Tervahartiala T, et al. Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children. Neuropathol Appl Neurobiol. 2006;32(3):304-17.
Lindberg, R. L., Sorsa, T., Tervahartiala, T., Hoffmann, F., Mellanen, L., Kappos, L., Schaad, U. B., Leib, S. L., & Leppert, D. (2006). Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children. Neuropathology and Applied Neurobiology, 32(3), 304-17.
Lindberg RL, et al. Gelatinase B [matrix Metalloproteinase (MMP)-9] and Collagenases (MMP-8/-13) Are Upregulated in Cerebrospinal Fluid During Aseptic and Bacterial Meningitis in Children. Neuropathol Appl Neurobiol. 2006;32(3):304-17. PubMed PMID: 16640649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gelatinase B [matrix metalloproteinase (MMP)-9] and collagenases (MMP-8/-13) are upregulated in cerebrospinal fluid during aseptic and bacterial meningitis in children. AU - Lindberg,R L P, AU - Sorsa,T, AU - Tervahartiala,T, AU - Hoffmann,F, AU - Mellanen,L, AU - Kappos,L, AU - Schaad,U B, AU - Leib,S L, AU - Leppert,D, PY - 2006/4/28/pubmed PY - 2006/7/6/medline PY - 2006/4/28/entrez SP - 304 EP - 17 JF - Neuropathology and applied neurobiology JO - Neuropathol Appl Neurobiol VL - 32 IS - 3 N2 - We investigated the protein expression of gelatinases [matrix metalloproteinase (MMP)-2 and -9] and collagenases (MMP-8 and -13) in cerebrospinal fluid (CSF) from patients with bacterial (BM, n = 17) and aseptic (AM, n = 14) meningitis. In both, MMP-8 and -9 were increased in 100% of patients, whereas MMP-13 was detectable in 53% and 82% respectively. Three patients with clinical signs of meningitis, without CSF pleocytosis, scored positive for all three MMPs. MMP-8 appeared in two isoforms, granulocyte-type [polymorphonuclear cell (PMN)] and fibroblast/macrophage (F/M) MMP-8. Analysis of kinetic changes from serial lumbar punctures showed that these MMPs are independently regulated, and correlate only partly with CSF cytosis or levels of the endogenous inhibitor, tissue inhibitor of matrix metalloproteinase-1. In vitro, T cells, peripheral blood mononuclear cells (PBMCs) and granulocytes (PMN) release MMP-8 and -9, whereas MMP-13 could be found only in the former two cell types. Using models of exogenous (n-formyl-Met-Leu-Phe, T cell receptor cross-linking) and host-derived stimuli (interleukin-2), the kinetics and the release of the MMP-8, -9 and -13 showed strong variation between these immune cells and suggest release from preformed stocks. In addition, MMP-9 is also synthesized de novo in PBMCs and T cells. In conclusion, invading immune cells contribute only partially to MMPs in CSF during meningitis, and parenchymal cells are an equally relevant source. In this context, in patients with clinical signs of meningitis, but without CSF pleocytosis, MMPs seem to be a highly sensitive marker for intrathecal inflammation. The present data support the concept that broad-spectrum enzyme inhibition targeting gelatinases and collagenases is a potential strategy for adjunctive therapy in infectious meningitis. SN - 0305-1846 UR - https://www.unboundmedicine.com/medline/citation/16640649/Gelatinase_B_[matrix_metalloproteinase__MMP__9]_and_collagenases__MMP_8/_13__are_upregulated_in_cerebrospinal_fluid_during_aseptic_and_bacterial_meningitis_in_children_ L2 - https://doi.org/10.1111/j.1365-2990.2006.00729.x DB - PRIME DP - Unbound Medicine ER -