Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis

Waubant, Emmanuelle; Goodkin, D E; Gee, Lauren; Bacchetti, Peter; Sloan, R.; Stewart, Thomas; Andersson, Peter-Brian; Stabler, G.; Miller, Karen

doi:10.1212/wnl.53.7.1397

Cited by 214 publications

(154 citation statements)

References 29 publications

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“…In addition, they play an important role in the fetal development, inflammatory cell migration and wound healing [27]. Under non-physiological conditions, MMPs are involved in tumour cell proliferation and dissemination [28] and in the pathophysiology of tissue-destructive diseases such as arthritis [29], multiple sclerosis [30] and central nervous system disorders [31]. MMPs, such as gelatinase B and collagenase, are mainly stored in the specific granules, whereas serine proteinases, such as elastase, proteinase 3 and cathepsin G, are located in azurophilic granules.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Moţa¹,

Moldovan²,

Călugăru³

et al. 2004

Scand J Immunol

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Human natural killer (NK) cells express low-affinity Fc immunoglobulin G (IgG) receptor (FcgRIIIA/CD16). The binding of monomeric IgG (mIgG) and F(ab 0 ) 2 fragments of 3G8 anti-CD16 monoclonal antibody (mAb) to FcgRIIIA was investigated by flow cytometry. Over 90% of NK cells bound endogenous IgG, and during incubation at 37 C, the FcgRIIIA occupancy decreased slowly. Approximately 90% of NK cells bind mIgG or F(ab 0 ) 2 fragments of 3G8 anti-CD16 mAb. The calculated half-time (T 1/2 ) of in vitro mIgG dissociation from FcgRIIIA was 130 min. By cross-linking the mIgG ligand with F(ab 0 ) 2 fragments of anti-human IgG antibody, the T 1/2 decreases to 85 min. In kinetics study, it has been shown that 125 I-mIgG bound to FcgRIIIA is slowly released in the culture supernatant, maybe eluted at acid pH, or partially internalized and degraded. The binding of IgG to FcgRIIIA was increased by 53.8% on cells cultured in the presence of RU36156, a matrix metalloproteinase (MMP) inhibitor. Furthermore, an increase in phosphorylation of Lyn tyrosine kinase, after cross-linking of mIgG-FcgRIIIA complex, was observed on NK cells treated with RU36156. When the FcgRIIIA was occupied by mIgG, the capacity of NK cells to kill K562 target cells was decreased by RU36156, because the MMP inhibitor protects CD16 from proteolysis. Our data demonstrate that binding of mIgG to human NK cells is followed by ligand dissociation and/or internalization, enzymatic degradation and exocytosis. The RU36156 MMP inhibitor protects FcgRIIIA from cleavage, augments NK-cell activation and may interfere in their killing capacity.

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Section: Discussionmentioning

confidence: 99%

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Moţa¹,

Moldovan²,

Călugăru³

et al. 2004

Scand J Immunol

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“…Treatment with highdose methylprednisolone for 3 days dramatically reduced the levels of MMP-9 in patients with evidence of BBB damage on Gadolinium-enhanced magnetic resonance imaging (MRI) (Rosenberg et al, 1996a). During an acute attack of multiple sclerosis, there is an increase in the levels of MMP-9 in the serum, but the source of the MMP-9 in the serum is uncertain (Waubant et al, 1999;Trojano et al, 1999;Lee et al, 1999). Treatment with interferon-␤ (IFN-␤) reduces the levels of mRNA for MMPs in the serum (Galboiz et al, 2001).…”

Section: Mmps In Neuroinflammation In the Absence Of Hypoxiamentioning

confidence: 99%

Matrix metalloproteinases in neuroinflammation

Rosenberg

2002

Glia

770

653

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Matrix metalloproteinases (MMPs) are a gene family of neutral proteases that are important in normal development, wound healing, and a wide variety of pathological processes, including the spread of metastatic cancer cells, arthritic destruction of joints, atherosclerosis, and neuroinflammation. In the central nervous system (CNS), MMPs have been shown to degrade components of the basal lamina, leading to disruption of the blood-brain barrier (BBB), and to contribute to the neuroinflammatory response in many neurological diseases. Brain cells express both constitutive and inducible MMPs in response to cellular stress. MMPs are tightly regulated to avoid unwanted proteolysis. Secreted as inactive enzymes, the MMPs require activation by other proteases and free radicals. The MMPs are part of a larger class of metalloproteinases (MPs), which includes the recently discovered ADAMs (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase thrombospondin) families. MPs have complex roles at the cell surface and within the extracellular matrix. At the cell surface, they act as sheddases, releasing growth factors, death receptors, and death-inducing ligands, making them important in cell survival and death. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the MMPs. Synthetic inhibitors have been developed for the treatment of arthritis and cancer. These hydroxymate-based compounds have been shown to reduce injury in experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), cerebral ischemia, intracerebral hemorrhage, and viral and bacterial infections. MPs have both beneficial and detrimental roles; understanding their expression in various CNS insults will allow for the use of MMP inhibitors in the treatment of neurological disorders. GLIA 39: 279 -291, 2002.

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“…MMP levels are increased in MS (Anthony et al, 1997;Cossins et al, 1997;Gijbels et al, 1992;Maeda and Sobel, 1996;Ozenci et al, 2000;Ozenci et al, 1999;Rosenberg et al, 1996;Sellebjerg et al, 2000;Trojano et al, 1999;Waubant et al, 1999) and in animal models of MS including experimental allergic encephalomyelitis (EAE) Gijbels et al, 1993;Graesser et al, 1998;Graesser et al, 2000;Jovanova-Nesic and Shoenfeld, 2006;Kieseier et al, 1998;Teesalu et al, 2001), and are very closely linked to pathogenesis and disease progression. Elevated serum MMP activity is detectable extremely early in the disease course, being present even in prodromal phases prior to development of clinically diagnosed MS (Correale and Bassani Molinas Mde, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Elevated serum MMP activity is detectable extremely early in the disease course, being present even in prodromal phases prior to development of clinically diagnosed MS (Correale and Bassani Molinas Mde, 2003). In relapsing-remitting MS, serum MMP activities are high during relapses and wax and wane in parallel with the disease course (Avolio et al, 2005;Kanesaka et al, 2006;Waubant et al, 1999). MMP-7 and -9 can be detected in active MS demyelinating lesions, with MMP-7 localized to microglia and invading macrophages .…”

Section: Introductionmentioning

confidence: 99%

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Cleavage of myelin associated glycoprotein by matrix metalloproteinases

Milward

Kim

Szklarczyk

et al. 2008

Journal of Neuroimmunology

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Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis

Abstract: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.

Cited by 214 publications

References 29 publications

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Interaction of Human Immunoglobulin G with CD16 on Natural Killer Cells: Ligand Clearance, FcγRIIIA Turnover and Effects of Metalloproteinases on FcγRIIIA‐Mediated Binding, Signal Transduction and Killing‡

Matrix metalloproteinases in neuroinflammation

Cleavage of myelin associated glycoprotein by matrix metalloproteinases

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