scholarly journals Binding of Pro-Matrix Metalloproteinase 9 by Fusobacterium nucleatum subsp. nucleatum as a Mechanism To Promote the Invasion of a Reconstituted Basement Membrane

2004 ◽  
Vol 72 (10) ◽  
pp. 6160-6163 ◽  
Author(s):  
Renée Gendron ◽  
Pascale Plamondon ◽  
Daniel Grenier

ABSTRACT In this study, we investigated the ability of Fusobacterium nucleatum subsp. nucleatum to increase its tissue-invasive potential by acquiring cell-associated human matrix metalloproteinase 9 (MMP-9) activity. Binding of pro-MMP-9 to fusobacteria was demonstrated by enzyme-linked immunosorbent assay. Zymography and a colorimetric assay showed that bound pro-MMP-9 can be converted into a proteolytically active form. The potential contribution of this acquired host activity in tissue invasion was demonstrated using a reconstituted basement membrane (Matrigel).

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ly Pham ◽  
Sydney O’Connor ◽  
Karen Yarbrough ◽  
Sven Jacobson ◽  
Barney J Stern ◽  
...  

Background: Elevated matrix metalloproteinase-9 (MMP-9) following acute ischemic stroke is associated with blood-brain barrier breakdown and hemorrhagic conversion. Prior retrospective evidence suggests that sulfonylurea use may be associated with reduced risk of hemorrhagic conversion. We hypothesized that sulfonylureas may reduce MMP-9 level in stroke patients. Methods: Using serial plasma samples from six subjects in the Glyburide Advantage in Malignant Edema and Stroke Pilot trial (GAMES-Pilot), we evaluated the level of MMP-9 in human subjects presenting with large hemispheric stroke who were treated with intravenous glyburide (RP-1127). MMP-9 was measured in a control cohort with large ischemic stroke who were not treated with glyburide. Commercially available ELISA kits and gel zymography were used to measure MMP-9 at baseline and at approximately 48 hours after stroke. GAMES subjects had additional time points analyzed until approximately 84 hours after stroke. Results: Average MMP-9 level in glyburide-treated stroke patients was 47.2 ± 8.0 ng/mL compared to 143.4 ± 60.35 ng/mL in untreated control subjects (p=0.004). Zymography analysis demonstrated a significant decrease in the pro-enzyme but no change in the active form of MMP-9. There was no difference in the level of the MMP-9 specific inhibitor, TIMP-1. No subjects exhibited parenchymal hemorrhagic conversion on 24 hour head CT scan. Conclusions: Glyburide treatment in human stroke patients with large hemispheric stroke is associated reduced level of MMP-9. Elucidating the underlying mechanism of glyburide’s effect on MMP-9 and the risk of hemorrhagic conversion may highlight future directions of therapy, including in combination with intravenous tissue plasminogen activator (IV t-PA).


Author(s):  
Diana Aguiar de Sousa ◽  
Maria Conceição Pereira-Santos ◽  
Ana Serra-Caetano ◽  
Lia Lucas Neto ◽  
Ana Luísa Sousa ◽  
...  

Abstract Background Elucidating mechanisms of brain damage in cerebral venous thrombosis (CVT) would be instrumental to develop targeted therapies and improve prognosis prediction. Matrix metalloproteinase-9 (MMP-9), a gelatinase that degrades major components of the basal lamina, has been associated to blood–brain barrier disruption. We aimed to assess, in patients with CVT, the temporal change in serum concentrations of MMP-9 and its association with key imaging and clinical outcomes. Methods Pathophysiology of Venous Infarction—PRediction of InfarctiOn and RecanalIzaTion in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Serial collection of peripheral blood samples performed on day 1, 3, and 8, and standardized magnetic resonance imaging on day 1, 8, and 90. MMP-9 was quantified using enzyme-linked immunosorbent assay in 59 patients and 22 healthy controls. Primary outcomes were parenchymal brain lesion, early evolution of brain lesion, early recanalization, and functional outcome on day 90. Results CVT patients with parenchymal brain lesion had higher baseline concentrations of MMP-9 compared with controls (adjusted p = 0.001). The area under receiver operating characteristic curve value for MMP-9 for predicting brain lesion was 0.71 (95% confidence interval [CI]: 0.57–0.85, p = 0.009). Patients with venous recanalization showed early decline of circulating MMP-9 and significantly lower levels on day 8 (p = 0.021). Higher MMP-9 on day 8 was associated with persistent venous occlusion (odds ratio: 1.20 [per 20 ng/mL], 95% CI: 1.02–1.43, p = 0.030). Conclusion We report a novel relationship among MMP-9, parenchymal brain damage, and early venous recanalization, suggesting that circulating MMP-9 is a dynamic marker of brain tissue damage in patients with CVT.


2007 ◽  
Vol 119 (1) ◽  
pp. S50-S51
Author(s):  
M. Suzukawa ◽  
A. Komiya ◽  
M. Iikura ◽  
H. Nagase ◽  
C. Yoshimura-Uchiyama ◽  
...  

2001 ◽  
Vol 116 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Claudia Felkel ◽  
Ulrike Schöll ◽  
Michael Mäder ◽  
Peter Schwartz ◽  
Klaus Felgenhauer ◽  
...  

2002 ◽  
Vol 8 (3) ◽  
pp. 222-228 ◽  
Author(s):  
G M Liuzzi ◽  
M Trojano ◽  
M Fanelli ◽  
C Avolio ◽  
A Fasano ◽  
...  

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (QAlb) and CSF/serum MMP-9 (QMMP-9) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of QMMP-9:QAlb (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.


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