Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation

Cobos-Correa, Amanda; Trojanek, Joanna; Diemer, S.; Mall, Marcus; Schultz, Carsten

doi:10.1038/nchembio.196

Cited by 100 publications

(92 citation statements)

References 21 publications

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“…After the elimination of cell content by centrifugation, probe 2 was simply added to the remaining BALf after sample dilution by a factor of two. In a mouse model of lung inflammation, Cobos-Correa et al detected, with a membrane-bound FRET probe, the active form of MMP-12 mostly on the surface of macrophages rather than in BALf (46). Here, with probe 2, active forms of MMP-12 were detected only in BALf.…”

Section: Discussionmentioning

confidence: 93%

Detection of Endogenous Matrix Metalloprotease-12 Active Form with a Novel Broad Spectrum Activity-based Probe*

Nury

Bregant

Czarny

et al. 2013

Journal of Biological Chemistry

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Background:The detection of MMP active forms remains a challenge. Results: An endogenous active form of MMP-12 was detected in animal fluids with a new activity-based probe. Conclusion:The presence of MMP active forms can be demonstrated only with a highly sensitive probe. Significance: It should be possible to validate active forms of MMP as potential biomarkers in different physiopathological contexts.

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Section: Discussionmentioning

confidence: 93%

Detection of Endogenous Matrix Metalloprotease-12 Active Form with a Novel Broad Spectrum Activity-based Probe*

Nury

Bregant

Czarny

et al. 2013

Journal of Biological Chemistry

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“…In this context, ongoing studies indicate that airway surface dehydration may cause activation of macrophages by particulates or irritants that are not properly cleared from mucostatic airways, causing elevated expression of macrophage elastase (matrix metalloprotease 12), which may be implicated in emphysema formation in bENaC-TG mice [30][31][32]. Notably, besides small airway mucus obstruction, early-onset emphysema has been reported as an early and invariable feature in the lungs of CF infants who died in the first year of life [3], highlighting the clinical importance of this phenotype in CF patients.…”

Section: Discussionmentioning

confidence: 99%

In vivomonitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography

Wielpütz¹,

Eichinger²,

Zhou³

et al. 2011

Eur Respir J

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The onset and spontaneous development of cystic fibrosis (CF) lung disease remain poorly understood. In the present study, we used volumetric computed tomography (VCT) as a new method for longitudinal in vivo monitoring of early lesions and disease progression in CF-like lung disease in b-epithelial Na + channel (ENaC)-transgenic (TG) mice.Using a VCT scanner prototype (80 kV, 50 mA?s, scan time 19 s and spatial resolution 200 mm), bENaC-TG mice and wild-type (WT) littermates were examined longitudinally at 10 time-points from neonatal to adult ages, and VCT images were assessed by qualitative and quantitative morphological parameters.We demonstrate that VCT detected early-onset airway mucus obstruction, diffuse infiltrates, atelectasis and air trapping as characteristic abnormalities in bENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in bENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in bENaC-TG compared with WT mice (median¡SEM -558¡8 HU in WT versus -686¡16 HU in bENaC-TG at 6 weeks of age; p,0.005).Our study demonstrates that VCT is a sensitive, noninvasive technique for early detection and longitudinal monitoring of morphological abnormalities of CF-like lung disease in mice, and may thus provide a useful tool for pre-clinical in vivo evaluation of novel treatment strategies for CF.

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“…In a very elegant study, COBOS-CORREA et al [73] investigated the presence of active MMP-12 in macrophages from BAL from mice exposed to ambient PM10. Using a ratiometric fluorescence resonance energy transfer reporter specific for MMP-12 (LaRee1) that is lipidated and targeted to the plasma membrane, they showed that active MMP-12 was present in the membrane of macrophages of animals instilled with the PM10.…”

Section: Particulate Mattermentioning

confidence: 99%

“…2) MMP-1 mRNA and protein expression can be induced via the MAPK ERK1/2, secondary to the action of NOX4 or b-arrestin (DEP exposure). 3) Active MMP-12 is located in macrophage membranes after exposure to PM10 [73].…”

Section: Mechanisms and Consequences Of Mmp Modulation By Air Pollutantsmentioning

confidence: 99%

Interaction of matrix metalloproteinases with pulmonary pollutants: Table 1–

Dagouassat¹,

Lanone²,

Boczkowski³

2012

Eur Respir J

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An air pollutant consists of any atmospheric substance that may harm humans, animals, vegetation or material. Various air pollutants have been reported, differing in their physicochemical characteristics. They can be grouped into four categories: gaseous pollutants (e.g. ozone, sulfur dioxide, oxides of nitrogen, carbon monoxide and volatile organic compounds), persistent organic pollutants, heavy metals (e.g. cadmium, lead and mercury) and particulate matter (coarse, fine and ultrafine). These pollutants can reach the respiratory system, eliciting pulmonary and/or systemic effects. These effects include inflammation, tissue remodelling and carcinogenesis: all phenomena where matrix metalloproteases (MMPs) play critical roles, given their broad effects on matrix remodelling and modulation of inflammation and cell signalling. Moreover, since expression and activity of MMPs can be induced by such stimuli, the hypothesis has been raised that MMPs could be involved in the health effects of pollutants. Until now, the implication of MMPs in these effects has been studied only for some pollutants and for a restricted selection of MMPs (mainly MMP-1, -2, -9 and -12), while evidence for a link between MMP induction/activation and health effects remains scarce. A larger number of studies is, therefore, needed in order to better understand the implication of MMPs in health effects associated with air pollution.

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Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation

Cited by 100 publications

References 21 publications

Detection of Endogenous Matrix Metalloprotease-12 Active Form with a Novel Broad Spectrum Activity-based Probe*

Detection of Endogenous Matrix Metalloprotease-12 Active Form with a Novel Broad Spectrum Activity-based Probe*

In vivomonitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography

Interaction of matrix metalloproteinases with pulmonary pollutants: Table 1–

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