Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Chaudhuri, Rekha; McSharry, Charles; Brady, Jeffrey D.; Donnelly, Iona; Grierson, Christal; McGuinness, Stephen; Jolly, Lisa; Weir, Christopher J.; Messow, Claudia-Martina; Spears, Mark; Miele, Gino; Nocka, Karl; Crowther, D; Thompson, Joyce; Brannigan, Maureen; Lafferty, Jane; Sproule, Michael; MacNee, William; Connell, Martin; Murchison, John T; Shepherd, Malcolm; Feuerstein, Giora; Miller, Douglas K.; Thomson, Neil C.

doi:10.1016/j.jaci.2011.12.996

Cited by 94 publications

(84 citation statements)

References 37 publications

(40 reference statements)

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“…Inappropriate expression and excessive activity of several matrix metalloproteinases (MMP), including MMP-9 [1,2] has been implicated in the tissue destructive processes associated with chronic lung diseases including COPD [2][3][4][5][6][7]. Increased sputum MMP-9 protein concentrations and/or activity are reported in current smokers with COPD compared to healthy smokers [8,9].…”

Section: Resultsmentioning

confidence: 99%

“…Long-term clinical trials of MMP-9 inhibitors in COPD would help establish whether blocking MMP-9 activity attenuates the development and progression of emphysema. Previously, we reported that sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by CT [7] suggesting that blocking both MMP-9 and MMP-12 may be more effective than inhibiting either MMP-9 or MMP-12 alone.…”

Section: Discussionmentioning

confidence: 96%

“…A cross sectional study was performed in subjects with COPD and healthy controls as part of the Glasgow COPD and Asthma Biomarker study [7]. Clinical, physiological and immunological plus imaging (COPD groups only) measurements were performed at baseline.…”

Section: Methods Subjectsmentioning

confidence: 99%

“…Lung volumes and diffusing capacity for carbon monoxide (DLco) were performed using the body box technique (Zan500 Body Plethysmography, nSpire Health Limited, Hertford, UK). Sputum induction was performed as previously described [7]. CT scans of the Chest were performed at full inspiration using 16 slice Brightspeed and 64 slice Lightspeed (GE CT scanner, Milwaukee, Wisconsin, USA) with the following parameters: 120 KV, 100 mAs, collimation 1mm, reconstruction slice thickness 0.65mm, reconstruction slice separation 0.5mm, pitch of 1 and the data was reconstructed with a CHST filter.…”

Section: Measurementsmentioning

confidence: 99%

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Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD

et al. 2013

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Background: Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD. Findings: In 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units). Sputum MMP-9 concentrations and mRNA expression in COPD subjects were significantly greater than in healthy never-smokers (p = 0.007 and p = 0.001 respectively) and similar to those in healthy smokers. Conclusions: Sputum MMP-9 concentrations in COPD are directly associated with the extent of emphysema measured by CT and MMP-9 expression levels are inversely associated with DLco. These findings support a role for MMP-9 in the pathogenesis of COPD.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Section: Methods Subjectsmentioning

confidence: 99%

Section: Measurementsmentioning

confidence: 99%

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Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD

et al. 2013

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“…MMP12 is overexpressed in smokers with COPD (8), and a specific SNP in the Mmp12 promoter associated with higher MMP12 activity has demonstrated faster FEV 1 decline in a cohort of current smokers with mild to moderate airway obstruction (13). A recent study examining MMP12 in COPD and asthma reported that, in patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, was directly associated with sputum MMP12 concentrations and activity (4).…”

mentioning

confidence: 99%

ExperimentalPneumocystislung infection promotes M2a alveolar macrophage-derived MMP12 production

Nelson

Christmann

Dunaway

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Among several bacterial and viral pathogens, the atypical fungal organism Pneumocystis jirovecii has been implicated as a contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In a previous study, we reported that Pneumocystis-colonized HIV-positive subjects had worse obstruction of airways and higher sputum levels of macrophage elastase/matrix metalloproteinase 12 (MMP12), a protease strongly associated with the development of COPD. Here, we examined parameters of Pneumocystis-induced MMP12 in the lungs of mice and its role in the lung immune response to murine Pneumocystis. Initial studies demonstrated that P. murina exposure induced Mmp12 mRNA expression in whole lungs and alveolar macrophages (AMs), which was dependent on the presence of CD4+ T cells as well as signal transducer and activator of transcription 6. Mmp12 mRNA expression was upregulated in AMs by interleukin (IL)-4 treatment, but downregulated by interferon (IFN)-γ, indicating preferential expression in alternatively activated (M2a) macrophages. IL-4 treatment induced the 54-kDa proenzyme form of MMP12 and the 22-kDa fully processed and active form, whereas IFN-γ failed to induce either. Despite a reported antimicrobial role in macrophage phagolysosomes, mice deficient in MMP12 were not found to be more susceptible to lung infection with P. murina. Collectively, our data indicate that MMP12 induction is a component of the P. murina-induced M2 response and thus provides insight into the link between Pneumocystis colonization/infection and exacerbations in COPD.

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Transcriptomics

Joseph¹

2022

Genomic and Epigenomic Biomarkers of Toxicology and Disease

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Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: Relationship to disease severity

Cited by 94 publications

References 37 publications

Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD

Sputum matrix metalloproteinase-9 is associated with the degree of emphysema on computed tomography in COPD

ExperimentalPneumocystislung infection promotes M2a alveolar macrophage-derived MMP12 production

Transcriptomics

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