Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study

Louhelainen, Noora; Stark, Harri; Mazur, Witold; Rytilä, Paula; Djukanović, Ratko; Kinnula, Vuokko L.

doi:10.1186/1471-2466-10-13

Cited by 40 publications

(31 citation statements)

References 40 publications

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“…Induced sputum analysis has found increases in MMP-9 protein and MMP-9 activity [83,85] in smokers with and without airflow obstruction. Interestingly, MMP-9 was increased in the sputum after smoking cessation compared to baseline, and this was not related to the numbers of neutrophils present [86]. Increased immunohistological staining of MMP-9 has been identified in the lungs of smokers with COPD [87] and in guinea pigs exposed to cigarette smoke [78].…”

Section: Series: Mmps In Lung Health and Diseasementioning

confidence: 86%

Matrix metalloproteinases in COPD

Churg

Zhou²,

Wright³

2011

Eur Respir J

240

116

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There is considerable evidence that matrix metalloproteinases (MMPs) are up-and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smokeinduced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.

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Section: Series: Mmps In Lung Health and Diseasementioning

confidence: 86%

Matrix metalloproteinases in COPD

Churg

Zhou²,

Wright³

2011

Eur Respir J

240

116

View full text Add to dashboard Cite

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“…Previous experimental COPD or emphysema models have been developed in guinea pigs. 14) mice, 36,37) rats, 38) and dogs 39) by exposing the animals to sulfur dioxide (SO 2 ), 17) smoke from solid fuel, 19) cigarette smoke, 14,24,42) lipopolysaccharide, 39) proteases and their secretagogues, such as PAE, PPE, NE, proteinase 3, MMP, 44,48,49) and the factors used can enhance the effect of each other. 50,51) However, the rat model seems to be more economical and more feasible, and smoke and bacterial infections appear to be the most frequently used initiators.…”

Section: Discussionmentioning

confidence: 99%

A Rat Model for Stable Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke Inhalation and Repetitive Bacterial Infection

et al. 2012

Biological & Pharmaceutical Bulletin

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To develop a stable chronic obstructive pulmonary disease (COPD) model in rats. Sprague-Dawley rats were treated with cigarette-smoke inhalation (CSI) for 12 weeks, repetitive bacterial infection (RBI) for 8 weeks, or the combination of the two (CCR) for 12 weeks and followed up for the additional 20 weeks. Tidal volume (V T ), peak expiratory flow (PEF) and 50% V T expiratory flow (EF 50 ), histological changes in the lungs, and levels of the cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-10 in serum and bronchial alveolar lavage fluid (BALF) were examined at intervals during the 32 week study period. The right ventricular hypertrophy index (RVHI) was also determined at the same times. V T , PEF, and EF 50 were decreased in rats with COPD compared to the control. The expression of TNF-α, IL-8 and IL-10 increased in both serum and BALF with a similar trend. Bronchiole and arteriole wall thickness and the degree of bronchiole stenosis and alveolar size increased in COPD rats. RVHI was reduced gradually following the treatment. All of these changes were more pronounced in the CCR-treatment group than in the other groups. Our results have shown that CSI or RBI alone can induce COPD in rats, but that the combination of CSI with RBI induces a stable COPD that has more similarity to complications seen in patients with COPD. This combination may therefore provide a more appropriate model for study of human COPD.Key words pulmonary disease; chronic obstructive; animal model; pulmonary function; histological change; right ventricular hypertrophy index Chronic obstructive pulmonary disease (COPD) has been defined as a preventable and treatable pathologic condition characterized by partially reversible airflow limitation, 1) and is a major cause of morbidity and mortality throughout the world.2) Its prevalence among the Chinese population aged 40 or older is 8.2%.3) Development of COPD is slow and progressive in humans, with occasional exacerbations caused by an inflammatory response to triggering substances such as noxious gases, 1) bacteria 4-6) or viruses. [7][8][9][10][11] Four abnormalities are present in chronic, stable COPD: emphysema, small airway remodeling, pulmonary hypertension, and chronic bronchitis.Tobacco smoking and bacterial infection are the most common and important risk factors for COPD, 1,12,13) and they have each been used to establish animal COPD models. [14][15][16] Animal models have also used other noxious gases [17][18][19] and Pneumocystis carinii infection 20) in COPD induction. Short term induction protocols (days) 17,21) have resulted in a pulmonary inflammatory infiltrate, increased mucus production, and pulmonary edema. Long term induction protocols (weeks or months) 15,[17][18][19] have produced, in addition to the inflammatory infiltrate, emphysema and pulmonary remodeling characterized by fibrosis, and thickened bronchiole and arterial walls. Problems with animal models are that most of them are of short duration and the COPD produced does not correspond to the late...

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“…The supernatant was frozen at -80uC for biochemical analyses. Cell viability was studied with trypan blue in a Burker chamber [23]. Cytocentrifuge preparations were made by Cytospin (Thermo Scientific, Wilmington, DE, USA) and centrifuged at 40536g for 6 min.…”

Section: Subjectsmentioning

confidence: 99%

“…Only the samples with ,70% of squamous epithelial cells were accepted for further assessments. The slides were frozen at -20uC [23].…”

Section: Subjectsmentioning

confidence: 99%

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

et al. 2013

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The pathophysiological features of chronic obstructive pulmonary disease (COPD)-asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells.Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n526), smokers (n523), asthma (n532), COPD (n539) and COPD-asthma overlap patients (n514).In patients with COPD-asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD-asthma overlap compared with COPD (p50.00016) and could be used to differentiate patients with overlap from those with COPD.Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD-asthma overlap. @ERSpublications Increased sputum levels of neutrophil gelatinase-associated lipocalin in COPD-asthma overlap versus COPD/asthma patients

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Elevation of sputum matrix metalloproteinase-9 persists up to 6 months after smoking cessation: a research study

Cited by 40 publications

References 40 publications

Matrix metalloproteinases in COPD

Matrix metalloproteinases in COPD

A Rat Model for Stable Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke Inhalation and Repetitive Bacterial Infection

Differences in plasma and sputum biomarkers between COPD and COPD–asthma overlap

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