MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation

Mercer, PF; Shute, Janis K.; Bhowmik, Angshu; Donaldson, Gavin C.; Wedzicha, JA; Warner, J O

doi:10.1186/1465-9921-6-151

Cited by 154 publications

(130 citation statements)

References 26 publications

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“…MMP-9 levels are increased in sputum (26) and bronchoalveolar lavage fluid (27) of asthmatic individuals and increase further in status asthmaticus (28). Furthermore, MMP-9 is also increased in other inflammatory obstructive lung diseases, such as in chronic obstructive pulmonary disease patients during exacerbations (29).…”

mentioning

confidence: 85%

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

Abel

Vliagoftis

2008

The Journal of Immunology

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Mast cells adhere to fibroblasts, but the biological effects of adhesion are not well understood. We hypothesized that these adhesive interactions are important for tissue remodeling through the release of matrix metalloproteinases (MMP). Murine bone marrow cultured mast cells (BMCMC) were cocultured with NIH-3T3 fibroblasts or murine lung fibroblasts (CCL-206) and supernatants analyzed for MMP-9 release by gelatin zymography. Coculture of BMCMC for 24 h with NIH-3T3 or CCL-206 fibroblasts increased the release of MMP-9 from fibroblasts by 1.7 ± 0.2 and 2.0 ± 0.7-fold, respectively. Coculture of BMCMC and fibroblasts in the presence of IgE increased further MMP-9 release, which was released by fibroblasts. MMP-9 release was dependent on TNF released from IgE activated BMCMC and on adhesive interactions between BMCMC and fibroblasts. Increased MMP-9 release was also p44/42-dependent, as was MMP-9 up-regulation during coculture of fibroblasts with resting BMCMC. Finally, IgE injection into the mouse ear increased MMP-9 content of the ear tissue in the absence of Ag, indicating that IgE-mediated remodeling may play a pathogenic role in allergic conditions even in the absence of exposure to allergens. In conclusion, mast cell-fibroblast interactions induce the release of proteases important for tissue remodeling, such as MMP-9. MMP-9 release was further increased in the presence of IgE during coculture, suggesting a role for mast cell-fibroblast interactions in atopic conditions.

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confidence: 85%

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

Abel

Vliagoftis

2008

The Journal of Immunology

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“…Notably, a recent study on smokers with and without COPD reveals that immunoreactivity for MMP-2 protein in peripheral lung tissue correlates with disease severity in patients with COPD rather than to cigarette smoking per se [18], which is fully in line with the current findings. Moreover, COPD patients display higher MMP-9 protein levels in the airways during exacerbations than during the stable phase of their disease [5] and ex-smokers with COPD colonised with bacteria display higher MMP-9 protein levels in the peripheral airways than noncolonised ex-smokers with COPD [19]. These observations, together with the observations in the current study, are all compatible with the idea that there is no pronounced impact on gelatinase mobilisation that occurs immediately after tobacco exposure in naïve airways and that such an impact requires repeated exposure to tobacco smoke over time as the pulmonary disease progresses, possibly also affected by co-factors such as infectious agents.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, an upregulation of MMP-9 and MMP-2 has been demonstrated in the lungs of patients with manifest chronic obstructive pulmonary disease (COPD), and an upregulation of MMP-9 has been detected in the lungs of patients with emphysema [3]. This upregulation of MMP may lead to an imbalance in the gelatinase homeostasis, especially if occurring in combination with a downregulation of TIMPs [4,5]. However, the course and order of proteolytic events preceding manifest COPD in tobacco smokers remain largely unknown.…”

mentioning

confidence: 99%

Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space

Glader

Eldh²,

Bozinovski³

et al. 2008

European Respiratory Journal

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Clinical studies have indicated increased gelatinase activity in the airways of patients suffering from chronic obstructive pulmonary disease caused by tobacco smoke. The present study aimed to determine whether acute exposure to tobacco smoke per se causes a substantial and lasting impact on gelatinases and their inhibitors in the peripheral airways of atopic and nonatopic human subjects.Bronchoscopy with bronchoalveolar lavage (BAL) was performed on occasional smokers with and without atopy before and after smoking 10 cigarettes over a 48-h period. Samples from a group of never-smokers not exposed to tobacco smoke served as controls. Gelatinase identity and activity were measured using zymography, and gelatinase activity assay and concentrations of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 were measured using ELISA.The results revealed no pronounced changes in identity, net activity or concentration of the gelatinases or changes in concentrations of TIMP-1 and TIMP-2 in BAL fluid before and after acute exposure to tobacco smoke.In conclusion, the present experimental study indicates that acute exposure to tobacco smoke does not cause any substantial impact on gelatinases or their inhibitors in the peripheral airways, irrespective of atopy status, a finding that is compatible with the fact that it takes many years of tobacco smoking to establish chronic obstructive pulmonary disease. KEYWORDS: Chronic obstructive pulmonary disease, macrophage, matrix metalloproteinase 9, neutrophils, tissue inhibitor of matrix metalloproteinase

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“…21 In addition, similar studies have observed that markers of the host response to tobacco smoke may be important predictors of COPD exacerbations and symptoms. [22][23][24] Inhaled corticosteroids that modify these markers of inflammation have been demonstrated to reduce the risk of COPD exacerbation. 25 Interestingly, among patients with severe COPD, inflammation has been demonstrated to persist years after smoking cessation, 26,27 and there are few data about whether modification in the rate of airflow obstruction is similar to those individuals with mild to moderate disease.…”

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confidence: 99%

The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations

et al. 2009

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BACKGROUND:Smoking cessation has been demonstrated to reduce the rate of loss of lung function and mortality among patients with mild to moderate chronic obstructive pulmonary disease (COPD). There is a paucity of evidence about the effects of smoking cessation on the risk of COPD exacerbations. OBJECTIVE:We sought to examine whether smoking status and the duration of abstinence from tobacco smoke is associated with a decreased risk of COPD exacerbations. DESIGN:We assessed current smoking status and duration of smoking abstinence by self-report. Our primary outcome was either an inpatient or outpatient COPD exacerbation. We used Cox regression to estimate the risk of COPD exacerbation associated with smoking status and duration of smoking cessation. PARTICIPANTS:We performed a cohort study of 23,971 veterans who were current and past smokers and had been seen in one of seven Department of Veterans Affairs (VA) primary care clinics throughout the US. MEASUREMENTS AND MAIN RESULTS:In comparison to current smokers, ex-smokers had a significantly reduced risk of COPD exacerbation after adjusting for age, comorbidity, markers of COPD severity and socioeconomic status (adjusted HR 0.78, 95% CI 0.75-0.87). The magnitude of the reduced risk was dependent on the duration of smoking abstinence (adjusted HR: quit<1 year, 1.04; 95% CI 0.87-1.26; 1-5 years 0.93, 95% CI 0.79-1.08; 5-10 years 0.84, 95% CI 0.70-1.00; ≥10 years 0.65, 95% CI 0.58-0.74; linear trend<0.001). CONCLUSIONS:Smoking cessation is associated with a reduced risk of COPD exacerbations, and the described reduction is dependent upon the duration of abstinence.

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MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation

Cited by 154 publications

References 26 publications

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

Mast Cell-Fibroblast Interactions Induce Matrix Metalloproteinase-9 Release from Fibroblasts: Role for IgE-Mediated Mast Cell Activation

Impact of acute exposure to tobacco smoke on gelatinases in the bronchoalveolar space

The Effects of Smoking Cessation on the Risk of Chronic Obstructive Pulmonary Disease Exacerbations

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